sort by

78 publications mentioning mmu-mir-302c

Open access articles that are associated with the species Mus musculus and mention the gene name mir-302c. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 305
In agreement with their in vitro expression pattern, the expression of miR-290 cluster miRNAs is already upregulated in four-cell stage mouse embryos and reaches the highest level in the blastocyst, whereas miRNAs of the miR-302 cluster begin expression later at E6.5 and reach their expression peak at E7.5 [4, 42, 43]. [score:12]
Because β-catenin could potentially regulate the expression of the miR-302 cluster indirectly by regulating the expression of Oct4, Sox2 or Nanog, we also tested for the expression of these transcription factors in the β-catenin knockdown ESCs. [score:11]
Interestingly, upon knockdown of β-catenin, the expression of all tested miR-302 cluster miRNAs dramatically decreased, whereas the expression of the miR-290 cluster miRNAs did not change, suggesting that β-catenin specifically regulates the expression of the miR-302-cluster miRNAs (Figure 2E). [score:9]
Although β-catenin is expressed early in mouse development, active Wnt signaling has only been detected in prestreak embryos from E6 onwards [15, 16] The activation of the Wnt pathway perfectly mirrors the increase in miR-302 gene expression, and thus, active Wnt/β-catenin signaling could be another missing factor that drives miR-302 expression in the mouse embryo. [score:8]
The miR-302 cluster is only expressed at moderate levels in mouse ESCs and shows a restricted expression pattern in the mouse embryo with exclusion from preimplantation stages; therefore, the regulation of miR-302 cluster miRNA expression is more complex than has been previously thought. [score:8]
To determine whether β-catenin regulates the expression of the two miRNA clusters, we knocked down β-catenin in mouse ESCs (Figure 2A,B) and analyzed the expression of the mature miR-302 and miR-290 cluster miRNAs by real time RT-PCR. [score:7]
Although it was clearly demonstrated that Oct4, Sox2 and Nanog regulate the expression of the miR-302 gene, the expression pattern of these pluripotency factors and the miR-302 gene only partially overlap [4]. [score:6]
Furthermore, expression of the miR-302 gene was further upregulated upon Wnt3a treatment in β-cat [flox/-]: CreER [T2] control cells treated with EtOH, but not in β-cat [flox/-]: CreER [T2] ESCs treated with Tam (Figure 4C). [score:6]
This result indicates that the decrease in miR-302 expression observed upon the knockdown of β-catenin is not caused by changes in the expression levels of these transcription factors. [score:6]
To determine whether expression of the miR-302 cluster miRNAs is driven by intrinsic Wnt signaling in ESCs, we treated the cells with Dkk1, an inhibitor of the Wnt signaling pathway. [score:5]
F,H, expression levels of the primary miR-302 transcript (pri-302), the β-catenin target gene Axin2 and pluripotency -associated genes were quantified using qRT-PCR experiments. [score:5]
To determine whether β-catenin directly regulates the expression of the miR-302 gene, we screened this promoter fragment for potential Tcf/Lef binding sites. [score:5]
miR-302 cluster miRNAs are downregulated in inducible β-catenin knockout ESCs. [score:5]
The miR-302 gene encodes a cluster of five microRNAs (miRNAs) (miR-302a/b/c/d and miR-367) that are highly expressed in human embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mouse embryonal carcinoma cells (e. g., P19 cells) and moderately expressed in mouse ESCs [1– 3]. [score:5]
As a control, treatment of the β-catenin [flox/-] ESCs with Tam, as expected, did not change the level of β-catenin protein nor the expression of the known β-catenin target Axin 2; β-actin; the pluripotency factor mRNAs Oct4, Sox2 or Nanog; or the miR-302 transcript (Figure 4B). [score:5]
In agreement, EOMES has been suggested to directly regulate expression on the miR-302 gene [14]. [score:5]
In Xenopus laevis embryos, the miR-302 ortholog miR-427 promotes mesendoderm formation by targeting the Lefties, inhibitors of the Nodal pathway [5]. [score:5]
In contrast, the expression of miRNAs of the miR-290 cluster did not change, indicating that Wnt signaling specifically activated expression of the miR-302 gene (Figure 3B). [score:5]
Thus, Oct4, Sox2 and Nanog are highly expressed in the blastocyst and beyond until E7.5, whereas the expression of the miR-302 gene is restricted to E6.5 and E7.5. [score:5]
The expression of both the primary transcript and the mature miRNAs of the miR-302 cluster, but not the miRNAs of the miR-290 cluster, were significantly downregulated when compared to the control cells (Figure 3C,D). [score:5]
However, a decrease in the expression of Nanog (although not significant) as seen in ESCs transfected with si β-cat 1 may further reduce miR-302 expression. [score:5]
Mutations in bs 8 did not abolish the activation of the miR-302 promoter fragment upon Tcf3 knockdown, whereas bs 5 and bs 6 mutations simultaneously abrogated the derepressive effect. [score:4]
It has been shown previously that the expression of the pri-miR-302 transcript is regulated by the binding of Oct4, Sox2 and Nanog to specific binding sites located in the promoter region of the miR-302 gene. [score:4]
In agreement with our results from the knockdown experiments, miR-302 gene expression was significantly reduced in the ESCs genetically ablated for β-catenin (Figure 4C). [score:4]
Expression of the miR-302 cluster is regulated by the Wnt pathway. [score:4]
miR-302 cluster miRNA expression is reduced in inducible β-catenin knockout ESCs. [score:4]
Wnt signaling regulates expression of the miR-302 cluster. [score:4]
Moreover, it has been suggested that the miR-302 gene might be a direct target of EOMES during the specification of the definitive endoderm [14]. [score:4]
β-catenin regulates expression of the miR-302 cluster in mouse ESCs and P19 cells. [score:4]
This cell line also showed reduced expression of both the mature miR-302 miRNAs and the pri-miR-302 transcript upon β-catenin knockdown (Figure 2G, H). [score:4]
These results further indicate that β-catenin regulates the expression of the miR-302 gene as the downstream effector of the Wnt pathway. [score:4]
To determine whether the expression of the miR-302 gene is regulated by Wnt signaling, we stimulated the Wnt pathway by treating mouse ESCs with Wnt3a. [score:4]
MiR-302 cluster miRNAs are downregulated in β-catenin -depleted cells. [score:4]
Reintroduction of the wildtype bs 5 and bs 6 into the promoter construct containing mutations in all eight candidate Tcf/Lef binding sites restored the responsiveness of this miR-302 promoter fragment to β-catenin knockdown and Wnt3a treatment (Figure 6A–C). [score:3]
In contrast, miR-302 cluster miRNAs are highly expressed in P19 cells, a cell line originally derived from an E7.5 embryo [1, 2, 30]. [score:3]
In mESCs derived from the E3.5 blastocyst, the miR-290 cluster miRNAs are expressed at much higher levels than the miRNAs of the miR-302 cluster [41]. [score:3]
In addition, reintroducing the wildtype bs 8 sequence into the miR-302 promoter construct that carried mutations in all eight candidate Tcf/Lef sites did not restore the responsiveness of this miR-302 promoter fragment towards the β-catenin knockdown or the Wnt3a treatment (Figure 6A–C). [score:3]
Members of the miR-302 and miR-290 clusters share the same seed sequence, and therefore, it has been proposed that they also share targets and act redundantly. [score:3]
Thus, it has been shown that the pluripotency factors Oct4, Sox2 and Nanog bind to the promoter region and drive the expression of the miR-302 cluster in human ESCs and in P19 cells [4, 13]. [score:3]
In summary, these results indicate that the expression of the miR-302 gene is under the control of the Wnt signaling pathway in mouse ESCs. [score:3]
It was shown that Tcf3 shares an overlapping set of target genes, including the miR-302 gene, with the pluripotency factors Oct4, Sox2 and Nanog in ESCs. [score:3]
In contrast to the miRNAs of the miR-302 cluster, however, the miRNAs of the miR-290 cluster did not alter their expression upon β-catenin depletion from mESCs or P19 cells. [score:3]
These assays revealed that three out of the eight candidate sites were important regulators of miR-302 expression. [score:3]
A,C, qRT-PCR analysis was performed to determine the expression levels of the primary miR-302 transcript (pri-302), Axin2 and Actb. [score:3]
Here, we identify the miR-302 gene as a new transcriptional target of the Wnt/β-catenin pathway in mESCs and P19 cells. [score:3]
Interestingly, mutations in the binding sites for Oct4 and Nanog also abolished the responsiveness of the miR-302 promoter fragment to β-catenin knockdown and Wnt3a treatment, suggesting that the Tcf/Lef and Oct4/Nanog binding sites interacted (Figure 6A–C). [score:3]
The miR-302 promoter contains non-canonical Tcf/Lef sites that drive expression of the miR-302 cluster miRNAs in a Wnt/β-catenin -dependent manner. [score:3]
Upon treatment, expression of both the pri-miR-302 transcript and the mature miRNAs increased up to three-fold (Figure 3A, B). [score:3]
An interdependence of the Tcf/Lef sites and the Oct4/Nanog sites is further supported by the specific expression pattern of the miR-302 cluster in the mouse embryo. [score:3]
In the mouse embryo, expression of the miR-302 cluster commences at embryonic day 6.5 (E6.5), peaks at E7.5 and decreases at E8.5 [4, 5]. [score:3]
Indeed, we found that the expression of the primary miR-302 transcript was significantly reduced in the β-catenin knockdown cells compared to cells transfected with a nonsilencing siRNA (Figure 2F). [score:3]
To determine whether β-catenin regulates the expression of the primary miR-302 transcript, we carried out real time RT-PCR experiments with primers detecting specifically the primary miR-302 transcript. [score:3]
Reintroduction of the wild type sequences of bs 5 and bs 6, but not bs 8, into the miR-302 promoter construct carrying mutations in all eight candidate Tcf/Lef sites restored the derepressive effect observed upon Tcf3 knockdown. [score:3]
The mature miRNAs of the miR-302 cluster are expressed as a polycistronic primary transcript. [score:3]
The expression of the miR-302 and miR-290 cluster miRNAs (also known as ESCC miRNAs) correlated with active β-catenin in ESCs, embryonic carcinoma cells and the developing mouse embryo (Figure 1A,B [4, 15]). [score:3]
Thus, expression of miR-302 cluster miRNAs rapidly and efficiently reprogram mouse and human fibroblasts to an iPS state without the need for exogenous transcription factors [8]. [score:3]
The simultaneous mutation of bs 5 and bs 6 completely abolished the responsiveness of the miR-302 promoter fragment to β-catenin knockdown or Wnt3a treatment. [score:3]
Three Tcf/Lef binding sites regulate the activity of the miR-302 promoter. [score:2]
In agreement with our previous results, β-catenin knockdown repressed the wildtype miR-302 promoter, whereas Wnt3a treatment activated this promoter (Figure 6A–C). [score:2]
This result suggests that transcription factors other than Oct4, Sox2 and Nanog may be additionally involved in the regulation of miR-302 transcription. [score:2]
In agreement with a repressive function of Tcf3, its knockdown increased the luciferase activity of the miR-302 fragment. [score:2]
C–E, luciferase assays were carried out in mESCs (C,D) or P19 cells (E) to examine the activity of the miR-302 promoter fragment with or without mutations in all eight candidate Tcf BS (C) or with mutations in BS 8 alone or BS 5 and BS 6 in combination (D,E) upon Wnt-3a treatment (R&D Systems; 150 ng/ml). [score:2]
were carried out to examine the activities of different pGL4.10-miR-302 promoter constructs upon β-catenin knockdown (A) or Wnt3a treatment (B,C) (Peprotech; 100 ng/ml). [score:2]
Our results on the regulation of the miR-302 promoter by Tcf3 further confirm this observation. [score:2]
This idea is supported by the fact that the responsiveness of the miR-302 promoter to β-catenin knockdown and the Wnt3a treatment was abolished not only when Tcf/Lef binding site bs 5 and bs 6 were mutated but also when the Oct4/Nanog binding sites were mutated. [score:2]
C, luciferase assays were performed to examine the activities of different pGL4.10-miR-302 promoter constructs upon Tcf3 knockdown. [score:1]
MiR-302 cluster miRNAs play important roles during the reprogramming of mouse and human somatic cells to pluripotency. [score:1]
Tcf3 binds to the miR-302 promoter and represses miR-302 transcription. [score:1]
Luciferase activity was minimal after transfection of the control pGL4.10 vector, whereas it increased strongly after transfection of the pGL4.10 vector containing the miR-302 promoter sequence (Figure 5C). [score:1]
As the only member of the Tcf/Lef family that demonstrated binding to the miR-302 promoter, Tcf3 bound to the bs 5 and bs 6 positions of the miR-302 promoter and repressed miR-302 transcription through these sites. [score:1]
The miRNAs from the miR-302 cluster, in addition to Wnt/β-catenin signaling, promote the formation of mesendoderm in the gastrulating embryo, whereas the loss of Tcf3 results in the expansion of axial mesoderm in the mouse [5, 15, 19]. [score:1]
To further determine whether Tcf3 represses the transcription of the miR-302 gene, we knocked down Tcf3 in mESCs by transfection of specific siRNAs and carried out luciferase assays (Figure 7C). [score:1]
A fragment of the miR-302 promoter containing the binding sites for OCT4, SOX2 and NANOG is sufficient to drive OCT4 -dependent activation of the miR-302-367 cluster in human ESCs and P19 cells [4]. [score:1]
We could not find enrichment for any of the activating Tcf/Lef factors on the miR-302 promoter, whereas the repressive factor Tcf3 was enriched at the -400 position of the miR-302 promoter where Tcf/Lef bs 5 and bs 6 were located. [score:1]
Several of the miR-302 and miR-290 cluster miRNAs share similar seed sequences, and it has been suggested that miRNAs of the two clusters act redundantly [12]. [score:1]
This idea is further supported by the fact that the miR-302 cluster functionally overlaps with the Wnt/β-catenin pathway. [score:1]
The responsiveness of the miR-302 promoter to Wnt/β-catenin signaling depends on Tcf BS 5 and Tcf BS 6 and the Oct4/Nanog BS. [score:1]
These non-canonical Tcf/Lef binding sites, which differed from the consensus sequence T/A-T/A-C-A-A-A-G by the change of G to C at the last position, were located within a cluster of binding sites for the pluripotency factors Oct4, Sox2 and Nanog in the miR-302 promoter (Figure 5A). [score:1]
0075315.g007 Figure 7Tcf3 binds to the miR-302 promoter in vivo and represses its activity. [score:1]
0075315.g005 Figure 5. A, schematic representation of the miR-302 promoter cloned into the pGL4.10 luciferase vector. [score:1]
In summary, these results show that Tcf3 binds to the miR-302 promoter and represses the transcription of the miR-302 gene through its interaction with the non-canonical Tcf/Lef binding sites 5 and 6. 10.1371/journal. [score:1]
For qPCR of the pri-miR-302 transcript, Absolute QPCR SYBR Green ROX Mix (Thermo Scientific) was used. [score:1]
Luciferase assays were carried out to examine the activities of different pGL4.10-miR-302 promoter constructs upon β-catenin knockdown (A) or Wnt3a treatment (B,C) (Peprotech; 100 ng/ml). [score:1]
0075315.g006 Figure 6The responsiveness of the miR-302 promoter to Wnt/β-catenin signaling depends on Tcf BS 5 and Tcf BS 6 and the Oct4/Nanog BS. [score:1]
MiRNAs of the miR-302 cluster have important functions in ESC biology and during reprogramming of somatic cells into iPSCs [6– 11]. [score:1]
Wnt/β-catenin mediated transcription of the miR-302 gene through two non-canonical Tcf/Lef binding sites bs 5 and bs 6 located in the miR-302 promoter. [score:1]
Oct4, Sox2 and Nanog are essential factors that bind to the miR-302 promoter and activate its transcription. [score:1]
The miR-290 cluster miRNAs may have important functions in mESCs and in vivo in the blastocyst, whereas miR-302 cluster miRNAs may be important at later stages. [score:1]
In summary, these results show that Tcf3 binds to the miR-302 promoter and represses the transcription of the miR-302 gene through its interaction with the non-canonical Tcf/Lef binding sites 5 and 6. 10.1371/journal. [score:1]
Altogether, these results indicate that bs 5 and bs 6 are the effectors of Wnt/β-catenin signaling in the miR-302 promoter. [score:1]
We cloned the miR-302 promoter fragment containing these sites into the pGL4.10 luciferase reporter vector and carried out luciferase experiments. [score:1]
Reintroducing miRNAs from the miR-302 or miR-290 clusters rescued the proliferation defect in these cells. [score:1]
Bs 5 and bs 6 are located within a cluster of binding sites for the pluripotency factors Oct4, Sox2 and Nanog in the miR-302 promoter. [score:1]
To determine which Tcf/Lef factors bind to the miR-302 promoter, we carried out chromatin immunoprecipitation (ChIP) experiments in mESCs and P19 cells (Figure 7 A, B). [score:1]
The miR-302 promoter fragment (positions -968 to +4) was cloned into the multiple cloning site of the pGL4.10 firefly luciferase reporter vector using the restriction enzymes XhoI and BglII. [score:1]
β-catenin might activate the transcription of the miR-302 promoter by a similar derepressive mechanism because, in our study, both the activating effect of β-catenin and Wnt3a as well as the repressive effect of Tcf3 was mediated by the Tcf/Lef binding sites bs 5 and bs 6. Moreover, mutating these binding sites under basal conditions resulted in an increase in luciferase activity, indicating that these sites were bound by a repressor. [score:1]
These results suggest that although bs 8 seemed to be important for the basal activity of the miR-302 promoter, it did not seem to be the effector of Wnt/β-catenin signaling. [score:1]
Tcf3 binds to the miR-302 promoter in vivo and represses its activity. [score:1]
A, schematic representation of the miR-302 promoter cloned into the pGL4.10 luciferase vector. [score:1]
Therefore, it was of general interest to determine whether, in addition to the miR-302 gene, the miR-290 gene was under the transcriptional control of the Wnt/β-catenin pathway. [score:1]
Here, we show that the Wnt/β-catenin pathway promotes transcription of the miR-302 cluster in mouse ESCs and P19 cells. [score:1]
[1 to 20 of 101 sentences]
2
[+] score: 146
Reprogramming via miR-302/367 might involve different pathways such as targeting several epigenetic factors that result in global demethylation of the genome, inhibition of Oct4 suppressor factors, and enhancement of pluripotency markers [28, 30– 33]. [score:7]
0127878.g001 Fig 1 Transduction and continuous expression of vectors were confirmed by injecting a GFP expressing empty lentiviral vector and lentiviral particle that included the miR-302/367+GFP cluster. [score:5]
Transduction and continuous expression of vectors were confirmed by injecting a GFP expressing empty lentiviral vector and lentiviral particle that included the miR-302/367+GFP cluster. [score:5]
miR-302/367 expressing lentiviral particles were injected into the mice striata to induce transdifferentiation of targeted cells into neuroblasts. [score:5]
The same pattern of GFP expression was detected when miR-302/367-GFP expressing lentiviral vectors were used. [score:5]
Regulation of somatic cell reprogramming through inducible mir-302 expression. [score:4]
The miR-302/367 cluster is involved in early embryonic development and expressed in NSCs. [score:4]
A regulatory circuitry comprised of miR-302 and the transcription factors OCT4 and NR2F2 regulates human embryonic stem cell differentiation. [score:3]
A few GFP [+]/NeuN [+] cells were detected within the brains of mice that received control vector+VPA (average cell count: day 7, 0.5; day 14, 8) or miR-302/367 expressing vector (average cell count: day7, 5; day 14, 6) (Fig 4A). [score:3]
The pluripotency genes, Oct4, Sox2 and Nanog increase the expression of miR-302/367 via binding to its promoter. [score:3]
In vitro reprogramming of human astrocytes into neuroblasts was determined by transfection of astrocytes with viral particles that expressed miR-302/367. [score:3]
0127878.g005 Fig 5 (A) Expressions of Oct4 and Nanog genes as pluripotent markers were not detected following miR-302/367+ valproic acid (VPA) treatment. [score:3]
Groups 5 and 6 received focal injections of viral particles that expressed the miR-302/367+GFP cluster and VPA injections as mentioned for groups 1 and 2. For astrocyte transplantation, 300,000 human astrocytes were concentrated in 3 μl of DMEM and transplanted into the mouse striatum two days after transfection. [score:3]
In order to prove in vivo conversion of astrocytes to neuronal cells, we transfected human cultured astrocytes with miR-302/367-GFP expressing viral particles which were subsequently transplanted into the striatum (Fig 6A). [score:3]
Human astrocytes were transduced with the miR-302/367+GFP expressing vector in vitro and then transplanted into mice striata. [score:3]
However, the combination of miR-302/367 and VPA resulted co -expression of DCX [+]/GFP [+] cells at both 7 and 14 dpi (Fig 3) which implied conversion of astrocytes into neuroblasts. [score:3]
0127878.g004 Fig 4 (A) received miR-302/367+GFP expressing vectors. [score:3]
Following in vitro neuronal induction of astrocytes by using the miR-302/367 cluster, some neuroblasts and neurons were detected that did not express GFP. [score:3]
which received both VPA and miR-302/367 expressing vector had higher numbers of GFP [+]/NeuN [+] cells especially at day 14 (average cell number: 39.33) (Fig 4). [score:3]
Morrisey et al. showed that the miR-302/367 cluster alone was enough to reprogram human fibroblasts to iPSCs, while the presence of valproic acid (VPA) as a histone deacetylase inhibitor was necessary for conversion of mouse fibroblasts to iPSCs by the miR-302/367 cluster. [score:3]
Interestingly, in a positive feedback loop miRNA-302/367 enhances the expression of the above mentioned reprogramming factors. [score:3]
Groups 5 and 6 received focal injections of viral particles that expressed the miR-302/367+GFP cluster and VPA injections as mentioned for groups 1 and 2. For astrocyte transplantation, 300,000 human astrocytes were concentrated in 3 μl of DMEM and transplanted into the mouse striatum two days after transfection. [score:3]
At six weeks after transfection of astrocytes with the miR-302/367 cluster, we checked for the expressions of markers of differentiated neurons. [score:3]
We used hematoxylin and eosin staining to assess the possibility of teratoma formation following local injection of the miR-302/367 cluster expressing lentiviral particles. [score:3]
At 24 hours after seeding, astrocytes were infected with GFP or miR-302/367-GFP expressing lentiviral particles and allowed to incubate overnight. [score:3]
The number of GFP [+] cells which expressed NeuN significantly increased in animals treated with the miR-302/367 cluster and VPA, especially at day 14. [score:3]
More than 80% of astrocytes became transduced with miR-302/367 and expressed GFP (Fig 6B). [score:3]
0127878.g007 Fig 7 (A) Human induced neurons expressed neuroblast marker [doublecortin (DCX)] and neuronal markers (TUJ1 and NeuN) at 8 and 10 days post in vitro (DPI) when they received the miR-302/367 cluster. [score:3]
We prepared the miR-302/367 cluster as lentiviral particles which included a GFP expressing sequence (System Biosciences, San Francisco, CA) by transfecting along with a Virapower Lentiviral Packaging Mix (Invitrogen) into 293T cells by the Lipofectamine 2000 Transfection Reagent (Invitrogen). [score:3]
Groups 3 and 4 received focal injection of viral particles that expressed the miR-302/367+GFP cluster. [score:3]
Administration of GFP and miR-302/367 expressing lentiviral particles into the striatum and the distribution of transduced cells. [score:3]
Following in vivo application of miR-302 we checked for the expression of pluripotency markers Oct4 and Nanog and did not detect positive cells. [score:3]
The administration of empty vector (GFP expressing vector) and/or miR-302/367 cluster vector did not cause the conversion of transfected (green) cells into neuroblasts during 2 weeks (Fig 3). [score:3]
The miR-302/367 cluster has been frequently reported as one of the highly expressed microRNAs in pluripotent stem cells [25– 29]. [score:3]
These induced neuroblasts could potentially generate neuronal cells; thus miR-302/367 might be considered a new tool for conversion of glial scar astrocytes to endogenous neuroblasts in repairing lesions for different neurological diseases. [score:2]
miR-302/376 induced neurons might be the result of pluripotent reprogramming of glial cells towards iPSCs and their subsequent differentiation to neuronal cells, or the result of direct conversion of astrocytes into neuroblasts. [score:2]
These results show that neuroblasts can be generated directly from adult human and mouse astrocytes by miR-302/367 -driven induction. [score:2]
Here we have shown that adult human astrocytes could be reprogrammed to neuroblasts by miR-302/367, both in vivo and in vitro. [score:1]
In vivo conversion of engrafted human astrocytes to neuroblasts by miR-302/367. [score:1]
Doublecortin (DCX [+]) cells were detected at 7 and 14 days post-injection (dpi) in animals pre -treated with VPA that afterwards received miR-302/367. [score:1]
Considering the previous reports on the effectiveness of Oct4, Sox2 and Nanog in inducing astrocytes into neurons, this positive loop may explain a possible mechanism for miRNA-302/367 induced neuronal fate from astrocytes [27, 28, 35]. [score:1]
Human astrocytes were converted into neurons by the miR-302/367 cluster in vitro, without pre-treatment with valproic acid (VPA). [score:1]
Here, we have shown high conversion of astrocytes to neuroblasts by miR-302/367 administered in conjunction with VPA. [score:1]
These data showed the neuronal differentiation of cells induced by miR302/367+VPA. [score:1]
Nine days after transduction of astrocytes with miR-302/376, immunofluorescence staining was performed to determine the fate of the engrafted cells. [score:1]
both miR302/367 and empty vector+VPA groups at day 14). [score:1]
Scale bar: 50 μm We showed that application of the miR-302/367 resulted in reprograming of adult mouse human astrocytes into neuroblasts both in vivo and in vitro. [score:1]
This data showed the conversion of induced human astrocytes to neuronal cells by miR302/367 alone. [score:1]
According to Fig 5A, we could not detected any Oct4 and Nanog positive cells in the sections obtained from mice treated with both the miR-302/367 cluster and VPA. [score:1]
0127878.g003 Fig 3Doublecortin (DCX [+]) cells were detected at 7 and 14 days post-injection (dpi) in animals pre -treated with VPA that afterwards received miR-302/367. [score:1]
Following focal administration of the miR-302/367 cluster into the striatum, we studied the fate of transfected cells by specific staining against doublecortin (DCX) as a neuroblast marker. [score:1]
Two months after miR-302/367 injections, the animals were perfused with PBS and paraformaldehyde, respectively and the sections were counterstained with hematoxylin and eosin. [score:1]
Although the astrocytes were the major transfected cells after in vivo injection of viral particles, other cell types might also receive miR-302/367 and undergo reprogramming. [score:1]
In vitro conversion of astrocytes to neuron-like cells by miR-302/367. [score:1]
In addition, we showed that human astrocytes could reprogram into neurons by the miR-302/367 cluster alone in neuronal differentiation medium. [score:1]
A number of cells transduced with the miR-302/367+GFP cluster following valproic acid (VPA) pre-treatment showed neuronal fate as determined by immunostaining against NeuN. [score:1]
Cells were prepared for electrophysiological recording at six weeks after transfection with the miR-302/367 cluster. [score:1]
We observed DCX, TUJ1 and NeuN positive cells in the miR-302/367+GFP treated cultures which implied conversion of astrocytes into neuroblasts and neuronal cells. [score:1]
miR-302/367 and valproic acid (VPA) converted the transducted cells into neuroblasts. [score:1]
Human astrocytes transduced with miR-302/367 produced neuroblasts in vitro as well as in vivo when engrafted into the adult mouse brain. [score:1]
Two months after injection of viral particles that expressed miR-302/367 and VPA, the striata areas were investigated for teratoma formation. [score:1]
[1 to 20 of 61 sentences]
3
[+] score: 116
Transfection of recipient TG6 cells with a mixture of Locked Nucleic Acid (LNA) probes, which specifically target the miR-302 cluster (mix LNA-302) (Supplementary Figure 1b), suppressed the miR-302-EXO effects, preventing the invalidation of the miR-302 targets (Figures 3e–g), increase of GFAP, repression of SHH pathway (Figures 3h and i) as well as the decrease of cell proliferation and clonal efficiency (Figures 3j and k). [score:7]
Luciferase expressing cells were co -injected with TG1 cells stably expressing scrambled sequence of the cluster miR-302 (TG1-scrb) or stably expressing the cluster miR-302. [score:7]
Expression of the miR-302 cluster in GSC promotes a paracrine tumor suppressor effect in vivoGBM are most often surgically removed. [score:5]
GSC expressing the miR-302 cluster represses SHH and SOX2 expression, proliferation and infiltration in a paracrine manner. [score:5]
To demonstrate that miR-302 expression in recipient TG6 cells was the result of the transfer from exosomes as opposed to endogenous synthesis, we inhibited the transcription by blocking the RNA polymerase II using actinomycin D. The blockade of the polymerase did not prevent the enrichment in miR-302 cluster in the recipient cells treated with miR-302-EXO, while it efficiently blocked the endogenous synthesis induced by the serum (Figure 3c). [score:5]
To assess whether GBM cells expressing the miR-302-367 cluster might affect the stemness state of naïve GSC in a paracrine manner, we harvested conditioned media from two different GSC primary cultures stably expressing the miR-302-367 cluster (TG1-miR-302 and GB1-miR-302) or a non-relevant construct (TG1-CRL and GB1-CRL). [score:5]
Expression of the miR-302 cluster in GSC promotes a paracrine tumor suppressor effect in vivo. [score:5]
These results indicate that miR-302 over -expression in GSC induced an efficient paracrine tumor suppressor effect on neighboring tumor cells. [score:5]
To probe the direct targeting of the 3′ untranslated region (3′UTR) of CXCR4 by the exosomal miR-302, we employed a luciferase reporter assay. [score:5]
In addition, our data indicate that a minor population of TG1-miR-302 cells (one TG1-miR-302 for five TG1-luc) was sufficient to suppress tumor development in vivo (Figures 4b and c). [score:4]
The mix miRCURY LNA Knockdown probes that target miR-302a, miR-302b, miR-302c and miR-302d were purchased from EXIQON (Madrid, Spain). [score:4]
As a result, the known targets of the mir-302 cluster such as CXCR4, SDF1, Cycline D1, Cycline A and E2F1 20, 21, 22, 23 were repressed in TG6 cells upon TG1-miR-302-EXO treatment (Figure 3d–f). [score:3]
After lentiviral infection, cell lines stably expressing the miR-302 cluster (TG1 cluster miR-302 and GB1 cluster miR-302) or the control shLuc-scb (TG1-CRL and GB1-CRL) were selected in blasticidin containing medium (1  μg/ml) for 15 days. [score:3]
In this context, we sought to assess whether the paracrine effect of miR-302 might act as a tumor suppressor in vivo by blocking tumor initiation and growth. [score:3]
Lysis of the TG6 recipient cells followed by qRT-PCR analysis revealed a strong increase in the expression level of all microRNAs members of miR-302 cluster. [score:3]
Quantification of miR-302-367 expression by q-RT-PCR in the supernatant and the pellet of exosome preparations from TG1/GB1-CRL or TG1/GB1-miR-302. [score:3]
We then treated a control GSC primary culture (stably expressing the red fluorescent protein, TG6-red fluorescent protein (RFP)) with TG1-miR-302 and GB1-miR-302 conditioned media and tracked the evolution of cell morphology over 4 days. [score:3]
After treatment the cells displayed a clear increase of GFAP expression and the repression of stem/progenitor markers such as SHH, SOX2 after 2 days and Nestin after 10 days following the addition of TG1-miR-302 or GB1-miR-302-derived exosomes (miR-302-EXO) (Figures 2e–g; Table 1). [score:3]
TG1-luc cells were injected alone as a control of tumor formation, together with TG1-miR-302 cells (at a ratio of one-to-one and five-to-one respectively) or together with TG1 cells expressing a non-relevant construct (TG1-scrb, control) (Figure 4a). [score:3]
Ten neurospheres from TG1-CRL and TG1-miR-302 cells stably expressing the RFP were seeded at the top surface of the MBS and cultured under air–liquid interface conditions for 3 weeks. [score:3]
Taken together, these results show that GSCs expressing the miR-302 cluster secrete molecules that efficiently altered the stemness state and repressed cell proliferation and tissue infiltration. [score:3]
Ex vivo tumorigenesis assay Ten neurospheres from TG1-CRL and TG1-miR-302 cells stably expressing the RFP were seeded at the top surface of the MBS and cultured under air–liquid interface conditions for 3 weeks. [score:2]
We have previously shown that miR-302 cluster neo-synthesis occurred few hours later after serum induction in GSC. [score:1]
Each member of the miR-302 cluster has been strongly detected by qRT-PCR in miR-302-EXO while weakly detected in the corresponding supernatant and undetected in similar preparation from TG1-CRL or GB1-CRL (CRL-EXO) (Figure 3a and Table 2). [score:1]
A similar construct lacking miR-302 binding elements (Δ3′UTR CXCR4-Luc) remained insensitive to the miR-302-EXO treatment (Figure 3g). [score:1]
In comparison, cells treated with CRL-EXO did not show any enrichment with the cluster miR-302. [score:1]
The seeded cells were regularly treated with either control or miR-302 conditioned medium. [score:1]
Furthermore, miR-302-EXO treatment induced a drastic decrease in the number of mitotic cells and the capacity of TG1 and TG6 cells to be clonal (Figures 2h and i). [score:1]
Overall, 10 cells were seeded in each well of 96-well plates containing control or miR-302 conditioned medium. [score:1]
TG1-miR-302 and GB1-miR-302 cells secrete exosomes capable to repress GSC stemness and proliferation. [score:1]
The luciferase activity of a reporter construct, which contained the 3′UTR of CXCR4 fused to the 3′ end of the luciferase coding sequence (Δ3′UTR CXCR4-Luc), was significantly reduced when the cells were treated with miR-302-EXO. [score:1]
Quantification of SHH, SOX2, NESTING immunofluorescence in naïve TG6 and TG1 treated during 2 days and 10 days by exosomes purified from TG1/GB1-CRL or TG1/GB1-miR-302. [score:1]
To assess the effects of miR-302 conditioned medium on GSC ability to infiltrate a cerebral tissue, we used organotypic cultures of mouse brain slices (MBSs). [score:1]
To assess the interactions between the exosomes and the recipient cells, we labeled TG1-miR-302-EXO with fluorescent lipophilic carbocyanine diIC16 and incubated naïve TG6 cells with the resulting fluorescent exosomes. [score:1]
The enrichment of recipient cells with the cluster miR-302 occurred within 15 min following the treatment with exosomes. [score:1]
The miR-302 cluster is transferred to neighboring cells via the secretion of exosomes. [score:1]
Following the exosome extraction from TG1 or GB1 conditioned media, we have assessed the presence of the miR-302 cluster in both the exosome pellet and the supernatant. [score:1]
However one-to-one as well as five-to-one ratio between TG1-luc and TG1-miR-302 cells altered tumor initiation, growth and the formation of infiltration foci (Figures 4b and c). [score:1]
Lentiviral particles were produced by transfecting the 293 T cell line with the 2K7BSD-Cluster mir-302 or 2K7BSD-shLuc-scb constructs along with the packaging vectors (Invitrogen, Waltham, USA). [score:1]
These results indicate that exosomes carrying miR-302 are able to rapidly deliver a high quantity of miR-302 cluster to the recipient cells. [score:1]
We purified the nanovesicles from conditioned media of either TG1 and GB1-CRL or TG1-miR-302 and GB1-miR-302 cells using Exoquick kit. [score:1]
Accordingly, TG1-miR-302 co-injection maintained mice survival while mice in the control group died within 100 days (Figure 4d). [score:1]
In comparison, 300-fold enrichment was obtained after only 15 min of miR-302-Exo treatment (Figure 3c and Supplementary Figure 1a). [score:1]
The secretion of these exosomes ensures the propagation of the miR-302 effects to neighboring naïve GSC. [score:1]
The treatment of naïve GSC with miR-302 conditioned medium strongly repressed the number of mitotic cells and impaired their ability to be clonal (Figures 1e and f). [score:1]
While TG6 cells, in the control conditions, confirmed their strong ability to invade and survive within the cerebral tissue, [20] the treatment with miR-302 conditioned medium repressed their ability to penetrate cerebral tissues. [score:1]
Importantly, although GSCs release vesicles of all sizes in their media, the nano-sized ones are efficient in promoting the miR-302-367 effects, since conditioned media depleted of small vesicles lost their capacity to induce the miR-302 effects on GSC (data not shown). [score:1]
Taken together, these results show that delivery of the miR-302 cluster is required to alter the stemness and proliferation properties of GSC. [score:1]
The rapid enrichment in the cluster miR-302 (15 min) indicates an external source of these microRNAs rather than internal neo-synthesis. [score:1]
[1 to 20 of 49 sentences]
4
[+] score: 94
By extension, it can be inferred that many common targets of miR-302 and miR-290 are likely to undergo similar differences in expression in tissues or cell types showing sex-related polymorphism of miR-302 expression, including EGs (Figure 3G) and, presumably, PGCs. [score:7]
These observations together with the results of the present study thus predicted that some shared targets of the miR-302 and miR-290 clusters should be specifically downregulated in male embryonic stem and germ cells, in which the miR-302 family accumulates at much higher levels than in female cells. [score:6]
Dataset S3 Predicted target transcripts from the Pictar target prediction software for miR-290 cluster (Sheet 1), miR-293 (Sheet 2), and miR-302 cluster (Sheet 3). [score:5]
To identify cellular targets of the miR-302 family, we used two different algorithms: Pic-Tar [41] and the EIMMo microRNA target prediction server (http://www. [score:5]
Dataset S2 Predicted target transcripts from the EIMMo target prediction software for miR-290 cluster (Sheet 1), miR-293 (Sheet 2), and miR-302 cluster (Sheet 3). [score:5]
1. Card DA, Hebbar PB, Li L, Trotter KW, Komatsu Y, et al. (2008) Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. [score:4]
Although some of these variations in expression between male and female ES cells could be attributed to differences in the rates of differentiation between the ES cell lines used, the greatest and most striking difference between the two sexes was observed at D5 with the miR-302 genomic cluster. [score:3]
In this context, identification of Arid4 as a novel target of both miR-290 and miR-302 is entirely consistent with the established role of ARID4 as an Rb -mediated repressor of E2F -dependent transcription, which is mandatory for the G1-S phase transition in the cell cycle [44]. [score:3]
Interestingly, all members of the miR-302 cluster share the same AAGUGC(U/C) 5′ seed sequence with the highly expressed members of the miR-290 cluster (with the notable exception, of course, of miR-293; Figure 2A–2B). [score:3]
We also used a miR-291a-3p duplex as a representative of the miR-290 family, of which several members are also predicted to target Arid4b owing to seed identity with miR-302 (Figure 4D, Dataset S2 and Dataset S3). [score:3]
To address this issue, we analyzed miR-302 expression in male and female pluripotent embryonic germ cells (EG) derived from PGCs that had been isolated at various stages of embryogenesis (8.5, and 9.5 dpc). [score:3]
Together with our ES cell time-course analysis (Figure 3B and 3D; Figure 4C) these results strongly suggest (i) that Arid4b is a common mRNA target of miR-302 and miR-290 family members and (ii) that the differences in Arid4b levels between male and female D2 and D5 ES cells are due to the male-specific accumulation of miR-302. [score:3]
This idea was recently given some experimental support by the demonstration that certain proliferation defects of Dgcr8 [−/−] mouse ES cells are rescued to a similar extent through ectopic expression of individual members of either the mouse miR-302 or miR-290 clusters [32]. [score:3]
The predicted target sites of miR-302 are indicated in red (7-mer) and blue (6-mers). [score:3]
Accordingly, ectopic expression of miR-302 is sufficient to reprogram human skin cancer cells into a puripotent ES-cell-like state [4]. [score:3]
These results thus suggested that any putative sex-specific embryonic expression of miR-302 should occur at earlier stages, before colonization of the gonads by primordial germ cells (PGC), which are also known to form during early ES cell differentiation (for a review, see [38]). [score:3]
The chromatin remo delling and E2F -dependent transcription repressors Arid4a and Arid4b are putative targets of miR-302. [score:3]
To examine further this male-specific differentiation miR-302 expression pattern, RNA from ES cells that had undergone differentiation for 10 days was also examined. [score:3]
The analysis finally unravelled a puzzling enrichment of miR-302 expression during male ES cell differentiation as well as in male embryonic germ cells, suggesting a contribution of this miR family to male germline determination. [score:3]
This highly dynamic and apparently sex-specific pattern suggested that the miR-302 family might have a role during a narrow window of male development. [score:2]
Male-specific regulation of the miR-302 gene in embryonic stem cells and germ cells. [score:2]
However, these slight changes could not account for the strong reduction in Arid4b protein levels in the same samples, thereby indicating an effect at the protein level consistent with a seed/3′-UTR type of regulation by the miR-302 family. [score:2]
These data can now be assembled into a comprehensive, albeit still speculative mo del, integrating the possible overlapping functions of miR-290 and miR-302 in mouse cell totipotency during early development (Figure S9). [score:2]
Figure S9Putative interactive mo del between miR-302 and miR-290 families and cell cycle regulation. [score:2]
Recent analyses in human ES cells indicate that the miR-302 promoter is directly activated by the Oct3/4, Sox2, and Nanog transcription factors, which are all required for pluripotency during early embryogenesis and for maintenance of embryonic stem cell identity [1]. [score:2]
Northern analyses of total RNA confirmed that the levels of miR-302d (one of the most frequently cloned representatives of the miR-302 cluster, Figure 3B, upper panel) are at least 20 fold higher in D5 male cells than in D5 female cells (Figure 3B, lower panel). [score:1]
Although this study involved a mixture of male and female embryos and thus, could not identify the sex-specific enrichment of miR-302 members, this profile resembles that of D2 and D5 female ES cells in our early differentiation system. [score:1]
Expression of the resulting construct was then measured in transfected human HEK-293 cells, which are devoid of miR-302 (data not shown). [score:1]
This suggests a strong and specific transcriptional enhancement of the miR-302 gene in male cells. [score:1]
Western Blot analysis at D0, D2 and D5 revealed a steady accumulation profile for the Arid4b protein throughout early differentiation of female mouse ES cells (Figure 4C, left panel), in which miR-302 levels remained low (Figure 3B–3C). [score:1]
We decided to focus on the Arid4b gene, whose 3′-UTR contains three evolutionary conserved matches for the seed shared by miR-302 and miR-290 (Figure 4A–4B). [score:1]
We are currently in the process of generating miR-302 conditional- deletion ES cells in order to produce miR-302 -deficient mice. [score:1]
This revealed that the increase in miR-302 observed at D5 in males is transient because it had decreased by D10 (Figure 3C). [score:1]
Binding sites for those transcription factors are highly conserved in the core promoter of mammalian miR-302 homologs, including in mouse [3]. [score:1]
Members of the miR-302 and miR-290 clusters can individually rescue the proliferation defects of mouse Dgcr8 [−/−] ES cells [32]. [score:1]
Further support for a male-specific enrichment of the miR-302 family came from Q-RT-PCR analyses showing that X [PGK]O ES cells (lacking a Y or a X chromosome) displayed only a very minor increase in miR-302d content, similar to female XX cells at D5 (Figure 3D). [score:1]
[1 to 20 of 36 sentences]
5
[+] score: 64
However, the pri-miR-302, pri-miR-181a-2 and pri-miR-181b-2 show upregulation in BIO- and CHIR -treated cells, this indicates that the reduced expression of mature miRNAs might be because of the inhibition of pri-miRNAs processing, rather than inhibition of miRNA transcription. [score:10]
qPCR results confirmed that BIO upregulated miR-302a-5p, miR-302b-5p, miR-302c-5p and miR-302d-5p (Fig. 3i) and that CHIR significantly downregulated the expression of miR-290-5p, miR-106a-3p, miR-106b-3p, miR-302b-5p, miR-302c-5p, and miR-93-5p (Fig. 3j). [score:9]
However, CHIR downregulated mature miR-302a, miR-302b, miR-302c, miR-181a and miR-181b expression, and BIO slightly downregulated miR-181a and miR-181b (Fig. 4e). [score:9]
The expression of pri-miR-302, pri-miR-181a-2, and pri-miR-181b-2 in β-catenin overexpressed J1 mESCs was determined by qPCR. [score:5]
β-catenin was overexpressed in J1 mESCs using the vector pCMV-Myc- β-catenin (Fig. 4a), and the expression of primary and mature forms of miR-302, miR-181a and miR-181b were determined by qPCR. [score:5]
qPCR results showed that BIO treatment resulted in a slight upregulation of pri-miR-302, pri-miR-181a-2 and pri-miR-181b-2. CHIR induced a higher level of expression of these primary miRNAs compared with BIO treatment (Fig. 4d). [score:5]
Consistently, pre-miR-302a, pre-miR-302b, pre-miR-302c and pre-miR-302d were reduced following CHIR treatment, and pre-miR-181a-2 and pre-miR-181b-2 were downregulated by both BIO and CHIR (Fig. 4f). [score:4]
The expression of miR-302a-5p, miR-302b-5p, miR-302c-5p, miR-181a-5p, and miR-181b-5p in β-catenin transfected J1 mESCs was determined by qPCR. [score:3]
The qPCR results showed that overexpression of β-catenin activates the transcription of pri-miR-302, pri-miR-181a-2 and pri-miR-181b-2 (Fig. 4b). [score:3]
The expression of miR-302a-5p, miR-302b-5p, miR-302c-5p, miR-181a-5p, and miR-181b-5p in BIO- or CHIR -treated J1 mESCs was determined by qPCR. [score:3]
The miR-302-367 cluster is comprised of miR-302b, miR-302c, miR-302a, miR-302d and miR-367, which are expressed specifically in pluripotent ESCs and mEC cells 23. [score:3]
Additionally, β-catenin overexpression increased the levels of mature miR-302a, miR-302b, miR-302c, miR-181a and miR-181b when compared with controls (Fig. 4c). [score:2]
Transcription of pri-miR-302, pri-miR-181a-2, and pri-miR-181b-2 in BIO or CHIR -treated J1 mESCs was determined by qPCR. [score:1]
To further analyse this, the precursor forms of miR-302a, miR-302b, miR-302c, miR-302d, miR-181a and miR-181b was examined by qPCR in J1 mESCs. [score:1]
for miR-302a, miR-302b, miR-302c, miR-302d, miR-181a and miR-181b were validated by qPCR (Fig. 3i and 3j). [score:1]
[1 to 20 of 15 sentences]
6
[+] score: 49
AFP mRNA expression was downregulated in the miR-302 transfected ADSCs by a mean factor of 0.521 (P < 0.001) (Figure 7(d)). [score:6]
Furthermore, transfection of the third-passaged ADSCs with miR-302 family resulted in upregulation of OCT4, Nanog, and Sox2 gene expression. [score:6]
48 hours after transfection, the expression levels of OCT4, Nanog, and Sox2 mRNAs in the miR-302 transfected ADSCs were significantly higher than the mock group, while the expression of AFP mRNA was reduced to about 50%. [score:5]
In the present study, third-passaged ADSCs were transfected with a recombinant vector expressing miR-302 cluster. [score:3]
Moreover, the effects of leukemia inhibitory factor (LIF) and ES cell-specific miRNA, miR-302 family [8], on the expression of pluripotency markers in mouse ADSCs were investigated. [score:3]
Moreover, Bar and colleagues [33] found that the most overexpressed miRNAs in undifferentiated human ES cells are miR-302b, miR-302c, miR-302d, miR-92b, miR-20b, miR-519d, miR-302a, miR-324-3p, miR-187, and miR-18b. [score:3]
48 hours after transfection, the expression levels of OCT4, Nanog, and Sox2 in miR-302 group were 1.834, 3.442, and 2.101 times higher than the mock group, respectively (P < 0.001, Figure 7(d)). [score:3]
Expression of Pluripotency Markers and AFP in the ADSCs after Transfection with miR-302 Family. [score:3]
The Effects of miR-302 on the Expression of Pluripotency Markers in the ADSCs. [score:3]
Figure 7(c) shows a significant increase in OCT4A protein expression in the miR-302 -transfected ADSCs. [score:3]
As previously indicated, the maintenance of ES cell identity significantly depends on the regulatory role of miR-302 cluster [34]. [score:2]
Since Brachyury and Pax6 were rarely detected in the third-passaged ADSCs (Figure 1(d)), we only compared the expression level of AFP mRNA between the miR-302 and mock groups. [score:2]
However, colony formation was not detected after transfection of the ADSCs with miR-302 family. [score:1]
Lin et al. [37– 39] successfully used miR-302/367 cluster to reprogram human hair follicle cells, melanocytes, and some cancer cell lines to iPS cells, while similar experiments have also been performed on mouse and human fibroblasts later [40– 42]. [score:1]
Third-passaged ADSCs were transfected with the pEGFPC1-miR-302 or mock vectors (ParsGenome). [score:1]
Third-passaged ADSCs were cultured in 6 cm tissue culture plates to reach 80% confluency, and then transfection with miR-302 (Figure 6(a)) or mock vectors was performed using Lipofectamine 2000. [score:1]
Transfection of the ADSCs with miR-302 Family. [score:1]
Transfection of Third-Passaged ADSCs with pEGFPC1-miR-302 Vector. [score:1]
In the pEGFPC1-miR-302 vector, the EGFP coding sequence and the precursor of miR-302a/b/c/d have their own CMV promoter (Figure 6(a)). [score:1]
[1 to 20 of 19 sentences]
7
[+] score: 34
The previous studies show that miR-302 inhibits the proliferation of endometrial cells with inhibiting CDK1 and Cyclin D1 expression in MCF7 and HepG2 [42, 43]. [score:7]
Transfectants of miR-302/367 cluster construct in UMUC3(shp100) cells also expressed a high level of miR-302d (Figure 4K) and inhibited Cyclin D1 expression in both UNUC3 (shp100) and p100−/− cells (Figure 4L and 4M). [score:7]
Our finding is supported by previous report that miR-302 expression suppresses Cyclin D1-CDK4/6 pathways [42]. [score:5]
These results demonstrate that miR-302 inhibits cyclin d1 3′-UTR luciferase activity, Cyclin D1 protein expression and cell cycle progression. [score:5]
To determine potential role of miR-302d in the Cyclin D1 expression, a miR-302/367 cluster construct was transfected into p100−/− cells and UMUC3 (shp100) cells, respectively. [score:3]
Construct expressing miR-302/367 was obtained from Addgene (Cambridge, MA). [score:3]
The p100-stimulation of CREB phosphorylation in its activation of LARP7/miR-302 transcription was convincingly demonstrated by using CREB knockdown in p100−/−(p100) cells. [score:2]
Constitutive expression of miR302 in UMUC3(shp100) cells induced G [0]/G [1] growth arrest as compared with UMUC3 (shp100/Vector) cells (Figure 4N). [score:2]
[1 to 20 of 8 sentences]
8
[+] score: 31
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-18a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-21, hsa-mir-23a, hsa-mir-31, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-96, hsa-mir-98, hsa-mir-99a, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-23b, mmu-mir-99a, mmu-mir-127, mmu-mir-128-1, mmu-mir-136, mmu-mir-142a, mmu-mir-145a, mmu-mir-10b, mmu-mir-182, mmu-mir-183, mmu-mir-187, mmu-mir-193a, mmu-mir-195a, mmu-mir-200b, mmu-mir-206, mmu-mir-143, hsa-mir-139, hsa-mir-10b, hsa-mir-182, hsa-mir-183, hsa-mir-187, hsa-mir-210, hsa-mir-216a, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-224, hsa-mir-200b, mmu-mir-302a, mmu-let-7d, mmu-mir-106a, hsa-let-7g, hsa-let-7i, hsa-mir-23b, hsa-mir-128-1, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-127, hsa-mir-136, hsa-mir-193a, hsa-mir-195, hsa-mir-206, mmu-mir-19b-2, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-23a, mmu-mir-31, mmu-mir-92a-2, mmu-mir-96, mmu-mir-98, hsa-mir-200c, mmu-mir-17, mmu-mir-139, mmu-mir-200c, mmu-mir-210, mmu-mir-216a, mmu-mir-219a-1, mmu-mir-221, mmu-mir-222, mmu-mir-224, mmu-mir-19b-1, mmu-mir-92a-1, mmu-mir-128-2, hsa-mir-128-2, mmu-mir-217, hsa-mir-200a, hsa-mir-302a, hsa-mir-219a-2, mmu-mir-219a-2, hsa-mir-363, mmu-mir-363, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-371a, hsa-mir-18b, hsa-mir-20b, hsa-mir-452, mmu-mir-452, ssc-mir-106a, ssc-mir-145, ssc-mir-216-1, ssc-mir-217-1, ssc-mir-224, ssc-mir-23a, ssc-mir-183, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-128-1, ssc-mir-136, ssc-mir-139, ssc-mir-18a, ssc-mir-21, hsa-mir-146b, hsa-mir-493, hsa-mir-495, hsa-mir-497, hsa-mir-505, mmu-mir-20b, hsa-mir-92b, mmu-mir-302b, mmu-mir-302d, hsa-mir-671, mmu-mir-216b, mmu-mir-671, mmu-mir-497a, mmu-mir-495, mmu-mir-146b, mmu-mir-708, mmu-mir-505, mmu-mir-18b, mmu-mir-493, mmu-mir-92b, hsa-mir-708, hsa-mir-216b, hsa-mir-935, hsa-mir-302e, hsa-mir-302f, ssc-mir-17, ssc-mir-210, ssc-mir-221, mmu-mir-1839, ssc-mir-146b, ssc-mir-206, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-128-2, ssc-mir-143, ssc-mir-10b, ssc-mir-23b, ssc-mir-193a, ssc-mir-99a, ssc-mir-98, ssc-mir-92a-2, ssc-mir-92a-1, ssc-mir-92b, ssc-mir-142, ssc-mir-497, ssc-mir-195, ssc-mir-127, ssc-mir-222, ssc-mir-708, ssc-mir-935, ssc-mir-19b-2, ssc-mir-19b-1, ssc-mir-1839, ssc-mir-505, ssc-mir-363-1, hsa-mir-219b, hsa-mir-371b, ssc-let-7a-2, ssc-mir-18b, ssc-mir-187, ssc-mir-218b, ssc-mir-219a, mmu-mir-195b, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, ssc-let-7d, ssc-let-7f-2, ssc-mir-20b-1, ssc-mir-20b-2, ssc-mir-31, ssc-mir-182, ssc-mir-216-2, ssc-mir-217-2, ssc-mir-363-2, ssc-mir-452, ssc-mir-493, ssc-mir-671, mmu-let-7k, ssc-mir-7138, mmu-mir-219b, mmu-mir-216c, mmu-mir-142b, mmu-mir-497b, mmu-mir-935, ssc-mir-9843, ssc-mir-371, ssc-mir-219b, ssc-mir-96, ssc-mir-200b
In our study, the putative porcine miR-302 cluster was highly expressed in both types of piPSCs, but hpiPSCs had a much higher expression level that was similar to that in EpiSCs. [score:5]
Regulation of somatic cell reprogramming through inducible mir-302 expression. [score:4]
This study demonstrated that overexpression of the whole porcine miR-106a-363 cluster and miR-302 cluster combined with OSKM improved the efficiency of piPSCs induction. [score:3]
Of note, the piPSCs highly expressing the miR-106a-363 cluster and putative porcine miR-302 cluster had enhanced reprogramming efficiency. [score:3]
This indicated that hpiPSCs dominantly expressed the miR-302 cluster. [score:3]
The miR-302 cluster regulates the PI3K-Akt signaling pathway, MAPK signaling pathway, TGF-β signaling pathway, lysine degradation and other processes (Fig 7B). [score:2]
It was previously reported that the miR-106a-363 cluster and miR-302 cluster promote reprogramming in mice by negatively regulating the TGF-β signaling pathway [35, 36]. [score:2]
The miR-106a-363 cluster and miR-302 cluster were both highly expressed in piPSCs compared with pEFs. [score:2]
Genomic location of the putative porcine miR-302 cluster. [score:1]
A putative porcine miR-302 cluster was predicted by miRdeep2. [score:1]
We observed that the number of AP -positive colonies was highest in the cells transfected with the putative miR-302 cluster group, then in those with the miR-106a-363 cluster group then in the control group (Fig 7E and Fig 7F). [score:1]
These findings indicate that the miR-106a-363 cluster and putative miR-302 cluster exhibited an improved reprogramming efficiency, which was consistent with the results observed in mouse cells. [score:1]
The miR-106a-363 cluster and putative miR-302 cluster therefore appear to have conserved functions in promoting the reprogramming efficiency in porcine cells. [score:1]
An approximately 1.5 kb range harboring the whole miRNA-106a-363 cluster and a 2 kb range containing the putative porcine miR-302 cluster were amplified. [score:1]
The pMXs system separately carrying the porcine miR-106a-363 cluster and putative porcine miR-302 cluster were used to reprogram the pEFs in combination with pMXs-Oct4, pMXs-Sox2, pMXs-Klf4 and pMXs-Myc (OSKM, laboratory stored). [score:1]
[1 to 20 of 15 sentences]
9
[+] score: 30
Electroporation of a polycistronic hsa-miR-302a/b/c/d cassette has reportedly led to human hair follicle cell reprogramming [22] through miR-302 -targeted cosuppression of 4 epigenetic regulators. [score:6]
As expected, the Pkm2 splicing isoform was significantly increased in miR200c and miR-302 transfected cells, however the effect was much more apparent in miR-369 transfected cells (Fig 5A and 5B), suggesting that miR369 directly targets SF expression of Pkm2. [score:6]
MicroRNA miR-302 inhibits the tumorigenecity of human pluripotent stem cells by coordinate suppression of the CDK2 and CDK4/6 cell cycle pathways. [score:5]
A combination of histone deacetylase 2 (HDAC2) suppression and lentiviral -mediated transfection of immature miR-302/367 sequences is reported to activate OCT4 expression and induce reprogramming. [score:5]
Regulation of somatic cell reprogramming through inducible mir-302 expression. [score:4]
Inhibition or reversion of epithelial–mesenchymal transition (EMT) was shown to be stimulated by miR-302 [20, 22, 24], -367 [20, 24], and -200c [23] during reprogramming, while TGF-β -mediated EMT signaling antagonized reprogramming. [score:3]
iPSCs reprogrammed by miR-302/367 displayed similar characteristics (e. g., pluripotency, marker expression, and teratoma formation) to those reprogrammed using OCT4, SOX2, KLF4, and cMYC in mouse cells, including chimera and germline contribution [20]. [score:1]
[1 to 20 of 7 sentences]
10
[+] score: 23
MiRNAs like miR-302 cluster mediate pluripotency [7, 23], and it thus was assumed that top over-expressed miRNAs such as miR-302 and miRNA-290-295 cluster in stem cells might directly or indirectly target pluripotent core factors [7, 23]. [score:7]
gov/gene/9759) (Fig.   7), including Mef2c (myocyte enhancer factor 2C), which was targeted by the top over-expressed miRNA clusters including miR-290-295 and miR-302 cluster (Fig.   7). [score:5]
Our results revealed that the top miRNAs such as miR-290 and miRNA-302 cluster do not directly target any core pluripotent factors during the pluripotent state (Fig.   4). [score:4]
Furthermore, the well-known miR-302 cluster and even a single miRNA, miR-294, also target modules functionally enriched in the developmental category with respectively corr p-value <1.4436E-21 (Fig.   3a- 3b), and corr p-value < 1.0157E-29 (Fig.   3c- 3d). [score:4]
Similarly, Many well-known miRNA clusters (e. g. miR-290-295 and miR-302) in stem cells also target Dnmt1 (Fig.   6c), an enzyme predominately responsible for methylation in hemimethylated CpG islands. [score:3]
[1 to 20 of 5 sentences]
11
[+] score: 21
Of these, 271 miRNAs were overexpressed in hESCs and 73 were overexpressed in HFF-1. The fifteen most significant miRNAs derived from eleven different hairpin precursors, all overexpressed in the hESC libraries, are shown in Table 2. Ten of these miRNAs belong to known hESC-specific miR-302/367 and miR-371/372/373 clusters. [score:7]
Seven of the significantly differentially expressed moRNAs were derived from the hESC-specific miR-302/367 cluster. [score:3]
Overexpression of miR-302 family members is able to reprogram human and mouse somatic cells to pluripotency [19, 20]. [score:3]
Most miRNAs deriving from the well-known pluripotency related miR-302/367, miR-371/372/373 and C19MC clusters were significantly overexpressed in our hESC data, a finding that is well in line with the earlier observations. [score:3]
miRNAs found in hESCs belong mostly to the miR-302 and miR-290 families expressed from miR-302/367 and miR-371–373 clusters, respectively [13, 14]. [score:3]
Among them are seven of the ten moRNAs that derive from the pluripotency related miR-302/367 cluster. [score:1]
One of those fluctuating TFs is NANOG [73], which is also involved in activation of ES cell miRNAs miR-290 and miR-302 [74]. [score:1]
[1 to 20 of 7 sentences]
12
[+] score: 21
Oct4 can bind directly to miR-302 and upregulate its expression [171], while canonical Wnt signaling regulates mir-302 expression involving 3 TCF/LEF binding sites. [score:10]
In the latter, knocking down β-catenin leads to decreased expression of mir-302, whereas knocking down Tcf3 produces the opposite effect [174], which promotes the expression of pluripotency genes in F9 and P19 cells [154, 175]. [score:7]
In one case this regulation involves the mir-302 gene, which encodes a cluster of 5 microRNAs (miRNAs) that are highly expressed in undifferentiated NTERA-2 cells and P19 cells [172, 173]. [score:4]
[1 to 20 of 3 sentences]
13
[+] score: 20
Other miRNAs from this paper: mmu-mir-302a, mmu-mir-302b, mmu-mir-302d
However, miR-302, miR-372, and miR-520a/520b/520e/520 h have been shown as tumor suppressors to inhibit cell growth or migration in various types of cancers such as breast, liver, and liver 22– 29. [score:5]
This result is supported by the role of the family member miR-302, which inhibits tumorigenicity of human pluripotent stem cells and regulates somatic cell reprogramming 33, 34. [score:4]
Differential expression of miR-302/372/373/520 family members in normal keratinocytes and HNC cell lines. [score:3]
To determine the potential role of the miR-302/372/373/520 family in HNC, the expression levels of 8 miRNAs (miR-302b, miR-372, miR-373, miR-520a, miR-520b, miR-520c, miR-520e and miR-520h) were examined in 4 normal keratinocyte cell lines and 6 HNC cell lines. [score:3]
Figure 1Differential expressions of miR-302/372/373/520 family members between normal keratinocytes and HNC cell lines. [score:3]
MiR-520b belongs to miR-302/372/373/520 family. [score:1]
However, it has been found that these miR-302/520 family members play diverse roles in different cancers 18– 29. [score:1]
[1 to 20 of 7 sentences]
14
[+] score: 20
Subsequently, Guo et al. showed that miR-290-295/miR-302 clusters downregulated apoptosis-promoting factors Bhlhe40, Casp8, Ikbkg, Perp, on the other hand, they also upregulated the apoptosis-inhibiting factor Aven under the condition of let-7c -induced apoptosis [30]. [score:9]
Wang Y miR-294/miR-302 promotes proliferation, suppresses G1-S restriction point, and inhibits ESC differentiation through separable mechanismsCell Rep. [score:5]
But miR-290-295 cluster is highly expressed in mESCs compare to the miR-302 cluster. [score:3]
There are ESC-specific miRNA clusters in human and mouse, such as miR-302 and miR-371-373 clusters in human embryonic stem cells (hESCs), miR-302 and miR-290-295 clusters in mESCs. [score:1]
However, recent studies showed that miR-290-295 and miR-302 clusters promote the rapid G1/S transition independent of the Rb family under normal growth conditions, but just under cytostatic conditions (nutrient deprivation and cell–cell contact) their promotive G1/S transition is Rb -dependent [41]. [score:1]
In fact, the miR-290-295 cluster is homolog of human miR-371-373, furthermore, the miR-302 and miR-290-295 clusters share the same seed sequence, as a result, they tend to have similar function in mESCs. [score:1]
[1 to 20 of 6 sentences]
15
[+] score: 20
Indeed, overexpressing ESCC miRNAs can improve reprogramming by replacing c-Myc [41], and expressing the miR-302 cluster is sufficient to reprogram a cancer cell line to cells expressing pluripotency genes [42]. [score:7]
However, we were unable to reproduce the result reported by Morrisey and colleagues [43] that expressing the miR-302/367 cluster alone is sufficent to reprogramme MEFs to iPSCs. [score:3]
In a dramatic show of miRNA's function in reprogramming, Morrisey and colleagues recently demonstrated that expressing the miR-302/367 cluster alone is sufficient to reprogramme mouse and human fibroblast cells to iPSCs [43]. [score:3]
We used the PB transposon where miR-302/367 cluster expression was controlled by the CAG promoter whereas in Morrisey's work, this cluster was delivered using a lentiviral vector. [score:3]
0040938.g002 Figure 2 a. Four microRNAs: miR302 (cluster), miR-25/93, miR-290 and miR-298 were able to improve reprogramming. [score:1]
Identification of miR-302 and miR-290 in our screen confirmed the previous studies [41], [42]. [score:1]
Four out of the 52 tested miRNAs or miRNA clusters: the miR-302 cluster, miR-25, miR-290 and miR-298, gave substantially more Puro [r] iPSC colonies (2–4 fold) than the control where only the four factors were used (PB-CAG-OCKS) (Fig. 2a). [score:1]
a. Four microRNAs: miR302 (cluster), miR-25/93, miR-290 and miR-298 were able to improve reprogramming. [score:1]
[1 to 20 of 8 sentences]
16
[+] score: 17
Recently, we reported that the expression of hES cell-specific miRNAs miR-302 d, miR-372 and miR-367 and miR-200c, as well as miR-199a, were strongly up-regulated by activin A [6]. [score:6]
The undifferentiated state of T3/HDF and T3/CMHDF, as well as T3/MEF and T3/CMMEF, cells was evidenced by the very high expression levels of "stemness" genes, as well as hES cell-specific miR-302/367 and miR-371/372/373 clusters, and low expression levels of differentiation markers of ectoderm, mesoderm and endoderm in addition to the strong staining of OCT4 and NANOG. [score:5]
The extremely abundant expression of hES cell-specific miR-302/367 and miR-371/372/373 clusters also indicated the very high proportion of undifferentiated hES cells present in these four cell populations. [score:3]
As demonstrated previously [24- 27], the miR-302/367 cluster on chromosome 4 and miR-371/372/373 cluster on chromosome 19 were extremely abundantly expressed in undifferentiated hES-T3 cells grown on T3HDF feeder (T3/HDF) and feeder-free Matrigel in T3HDF-conditioned medium (T3/CMHDF), as well as MEF feeder (T3/MEF) and feeder-free Matrigel in MEF-conditioned medium (T3/CMMEF). [score:3]
[1 to 20 of 4 sentences]
17
[+] score: 16
Furthermore, qPCR was performed again to validate the downregulated and upregulated expression of selected miRNAs that may be relevant to development and confirmed that miR-135, miR-302, miR-449a, miR-200b, miR-200c, miR-193b, miR-130, and miR-141 were downregulated, whereas miR-10a, miR-181, and miR-470 were upregulated by RA treatment (Fig 4C and 4D). [score:16]
[1 to 20 of 1 sentences]
18
[+] score: 16
However, BMP4 was up-regulated by AICAR addition; therefore, the reduced miR-302 cluster expression may have resulted from increased BMP4 expression. [score:8]
Those down-regulated miRNAs included miR-134-5p, miR-296-3p, miR-381-3p, miR-449a-5p, miR-449c-5p, and miR-302 clusters. [score:4]
MiR-302 has been demonstrated to be inhibited by BMP4. [score:2]
Mir-302 clusters are abundantly expressed in human ES cells and functioned in ES cell pluripotency maintenance and self-renewal [24]. [score:2]
[1 to 20 of 4 sentences]
19
[+] score: 15
In fact, miR-302 and miR-372 have been shown to promote reprogramming, and miR-302 and miR-372 inhibit the TGF-ß -induced epithelial–mesenchymal transition, as does mouse miR-294 [37]. [score:3]
Eigenvectors with absolute values greater than 2 are shown in Table 2. Most of the listed miRNAs are members of the miR-302 cluster and two human-specific C19MC clusters (the miR-371/372/373 and miR-512∼ clusters), and these miRNAs were previously reported to be expressed in ES and iPS cells [10], [12]– [16], [30], [31]. [score:3]
In addition, other miRNAs—such as miR-17, -20a, -93, -106b, -106a, and -20b, and miR-302 members—which share the same sequence as the miR290 cluster, the miR-371 cluster, and C19MC, and were detected at high levels in both human and mouse ES/iPS cells, were shown to mediate reprogramming by targeting Tgfßr2 and p21 during the mesenchymal-to-epithelial transition during the initiation stage of reprogramming [6]. [score:3]
The miRNAs, reported in numerous studies and expressed abundantly in human and mouse pluripotent cells, are members of the miR-302 cluster [12], [13], [15], [16]. [score:3]
The seed sequence of miR-302 is identical to those of miR-372, miR-373 [39], [40], and some C19MC members. [score:1]
Members of the miR-302 cluster were ranked 11 [th], 17 [th], 34 [th], and 59 [th] in the mouse list, and 1 [st], 30 [th], and 33 [rd] in the human list. [score:1]
In addition, miR-367, which is a distantly related member of the miR-302 cluster [36], was 37 [th] in the mouse list and 17 [th] in the human list. [score:1]
[1 to 20 of 7 sentences]
20
[+] score: 15
Other miRNAs from this paper: hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-21, hsa-mir-23a, hsa-mir-100, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, mmu-mir-1a-1, mmu-mir-23b, mmu-mir-125b-2, mmu-mir-130a, mmu-mir-9-2, mmu-mir-145a, mmu-mir-181a-2, mmu-mir-184, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-205, mmu-mir-206, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-199a-2, hsa-mir-205, hsa-mir-181a-1, hsa-mir-214, hsa-mir-219a-1, hsa-mir-223, mmu-mir-302a, hsa-mir-1-2, hsa-mir-23b, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-184, hsa-mir-206, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-21a, mmu-mir-23a, mmu-mir-103-1, mmu-mir-103-2, rno-mir-338, mmu-mir-338, rno-mir-20a, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-107, mmu-mir-17, mmu-mir-100, mmu-mir-181a-1, mmu-mir-214, mmu-mir-219a-1, mmu-mir-223, mmu-mir-199a-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-181b-1, mmu-mir-125b-1, hsa-mir-302a, hsa-mir-219a-2, mmu-mir-219a-2, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, hsa-mir-372, hsa-mir-338, mmu-mir-181b-2, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-16, rno-mir-17-1, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-100, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-125b-1, rno-mir-125b-2, rno-mir-130a, rno-mir-145, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-184, rno-mir-199a, rno-mir-205, rno-mir-206, rno-mir-181a-1, rno-mir-214, rno-mir-219a-1, rno-mir-219a-2, rno-mir-223, hsa-mir-512-1, hsa-mir-512-2, rno-mir-1, mmu-mir-367, mmu-mir-302b, mmu-mir-302d, rno-mir-17-2, hsa-mir-1183, mmu-mir-1b, hsa-mir-302e, hsa-mir-302f, hsa-mir-103b-1, hsa-mir-103b-2, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, rno-mir-219b, hsa-mir-23c, hsa-mir-219b, mmu-mir-145b, mmu-mir-21b, mmu-mir-21c, mmu-mir-219b, mmu-mir-219c, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
For example, the cluster of miR-512-3p, miR-205, and the miR-302 family illustrated on the heat map demonstrates high expression in undifferentiated ES and early neural progenitor stages, downregulation during the glial restricted and early OP transitions, but then additional high expression during mid to late OP development. [score:9]
From the top ten downregulated miRNAs at this transition, six miRNAs (miR-367, miR-302a, miR-302c, miR-372, miR-302b, and miR-302d) have been shown to encourage proliferation and are highly expressed in undifferentiated cells and cancer stem cells [43], [44], [45], [46], [47], [48]. [score:6]
[1 to 20 of 2 sentences]
21
[+] score: 14
In our study, the Dgcr8 [Δ/Δ] fibroblasts lacked miRNAs both promoting reprogramming, such as the miR-290s and miR-302s, and inhibiting reprogramming, such as the let-7s; however, the fibroblasts used by Zhang et al. (2013) were only deficient in the reprogramming-promoting miR-302/367 cluster. [score:3]
Recent work has demonstrated that miRNAs such as miR-294, miR-302, and miR-181 family members facilitate (Judson et al., 2013, Li et al., 2011, Liao et al., 2011, Lin et al., 2011, Melton et al., 2010, Subramanyam et al., 2011), but let-7 family members inhibit, reprogramming (Melton et al., 2010, Unternaehrer et al., 2014). [score:3]
Together with the Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC) (Takahashi and Yamanaka, 2006), co -expression of the miRNA cluster 302/367 or 106a/363; members of the miR-302, miR-294, or miR-181 family; or miR-93 and miR-106b greatly enhance iPSC derivation efficiency (Judson et al., 2013, Li et al., 2011, Liao et al., 2011, Lin et al., 2011, Subramanyam et al., 2011). [score:3]
Furthermore, expression of the miR-302/367 cluster or miR-200c, miR-302, and miR-369 without the Yamanaka factors is sufficient to reprogram human and mouse fibroblasts (Anokye-Danso et al., 2011, Miyoshi et al., 2011). [score:3]
These data suggested the miR-302/367 cluster is required for human somatic cell reprogramming. [score:1]
Recently, Zhang et al. (2013) reported that they were unable to isolate iPSCs from human foreskin fibroblasts that were null for the endogenous miR-302/367 cluster. [score:1]
[1 to 20 of 6 sentences]
22
[+] score: 14
MicroRNA miR-302 inhibits the tumorigenecity of human pluripotent stem cells by coordinate suppression of the CDK2 and CDK4/6 cell cycle pathways. [score:5]
Regulation of somatic cell reprogramming through inducible mir-302 expression. [score:4]
S2 Fig A, Fluorescent TUNEL staining was performed to detect apoptotic HT29 cells transfected with miR302, miR302 plus miR-369s, or negative control (NC) miR. [score:1]
C, of the apoptosis-related proteins Bak, Bid, Bcl-xl, Bcl2, Mcl1, Caspase-8, and Caspase-3 in HT29 and DLD-1 cells transfected with miR302, miR-369s, miR302 plus miR-369s, or NC miR. [score:1]
miR302 -transfected DLD-1 colorectal cancer cells were analyzed for DNA methylation. [score:1]
B, Propidium iodide and Annexin V-FITC staining was performed in DLD-1 cells 60 h post-transfection with miR302, miR-369s, miR302 plus miR-369s, or NC miR. [score:1]
To prepare a CA transfection mixture in vitro, 2 μg of each miR-302 (-a,-b,-c,-d), miR-369 (-3p,-5p) or NC miR was mixed with 4 μL of 1 M CaCl [2] in 1 mL of serum-free bicarbonate (44 mM)-buffered DMEM medium (pH 7.5) incubated at 37°C for 30 min, and used for transfection [15– 17]. [score:1]
[1 to 20 of 7 sentences]
23
[+] score: 14
Faherty N Curran SP O’Donovan H Martin F Godson C Brazil DP CCN2/CTGF increases expression of miR-302 microRNAs, which target the TGFβ type II receptor with implications for nephropathic cell phenotypesJ Cell Sci. [score:5]
Our findings also demonstrate that miR-299, miR-499, miR-302, and miRNA-200 were upregulated in EPO-MVs (Fig.   8c). [score:4]
The miRNA profiles of the MVs revealed that EPO-MVs changed 212 miRNAs (fold-change ≥ 1.5), including miR-299, miR-499, miR-302, and miRNA-200, and that 70.28 % of these changes involved upregulation. [score:4]
miR-302 decreases TGF-β1 -induced EMT in renal HKC8 epithelial cells and attenuates the TGF-β1 -induced mesangial production of fibronectin and thrombospondin [44]. [score:1]
[1 to 20 of 4 sentences]
24
[+] score: 13
miR-302 has also been reported to suppress p63 expression in germ cells [48], while iASPP protein inhibits the expression of miR-574-3p and miR-720, which in turn inhibits p63 expression [49, 50]. [score:13]
[1 to 20 of 1 sentences]
25
[+] score: 13
Expression of the miR-302 cluster was highly ES-specific (Fig. 3c); levels of miR-302 miRNAs were downregulated upon HRas/Q61L induction, and further decreased in BD-TS cells. [score:6]
We began by analyzing expression of the miR-290, miR-302, and miR-17∼92 clusters in staged embryos. [score:3]
We compared expression of miRNAs from three different ESC -associated miRNA clusters: (miR-302 cluster [44]; miR-290 cluster [23]; miR17-92 cluster [45]) in iRas-Dox, iRas+Dox_48 h, and BD-TS cells. [score:2]
The miR-302 cluster was not detected at appreciable levels in the embryos profiled. [score:1]
c) miR-302 cluster (miRNA 302a, 302b, 302c, 302d, 367). [score:1]
[1 to 20 of 5 sentences]
26
[+] score: 13
Ubiquitously expressed miR-16, miR-21, and miR-212 were used as positive controls, and did not show any significant differences between wt, mdx and tg serum, whereas miR-122a and miR-323 which expressed specifically in liver and brain, respectively, and miR-302 did not dectect in all of EVs (S3B Fig). [score:5]
Ubiquitously expressed miR-21, mir-29, and small nucleolar RNA 202 (sno202) were used as positive controls, and did not show any significant differences between wt, mdx and tg serum, whereas miR-302, which specifically expressed in embryonic stem cell, did not detect in all of sera (S1A Fig). [score:5]
miR-302 is specifically expressed in embryonic stem cell. [score:3]
[1 to 20 of 3 sentences]
27
[+] score: 11
The miR-302/367 family is involved in multiple kinds of diseases, including tumors, immune diseases, cardiovascular diseases, and so forth [32– 34]. [score:7]
Subramanyam D Lamouille S Judson RL Liu JY Bucay N Derynck R Blelloch R Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cellsNat Biotechnol. [score:3]
miR-302b is a member of the miR-302/367 family. [score:1]
[1 to 20 of 3 sentences]
28
[+] score: 10
Many of the miRNAs in this cluster share the hexamer seed ‘AAGUGC,’ which is also expressed at much lower levels by the mir-302 and mir-467 clusters, contributing less than 5% of total reads (Table S2). [score:3]
Table S2Sequences and expression level of the mir-302, mir-467, and mir-17-92 clusters in ES cells. [score:3]
Because deletion of Dcr involves global miRNA loss, and three additional clusters containing the same or similar hexamer seed, mir-302, mir-467, and mir-17-92, are expressed in ESCs (Table S2), we examined the 295 KO line to determine the specific contribution of the mir-295 cluster to cell survival. [score:3]
In this context, the Casp2 reporter was derepressed approximately half as strongly as it was in Dcr KO cells, suggesting that the miR-302 and miR-467a families of miRNAs incompletely compensate for loss of the mir-295 cluster (Figure 5A). [score:1]
[1 to 20 of 4 sentences]
29
[+] score: 10
In addition, miR-302 and miR-467a are expressed in mouse ES cells and supplement silencing of the miR-290–295 targets via the 2–7 U seed [16], [27]. [score:5]
The miR-302 cluster is the most abundant miRNA family in human ES cells, and appears to be mostly responsible for 2–7 U seed functions instead of miR-371–373, which is expressed at much lower levels [12]. [score:3]
This seed is shared with miRNAs that are otherwise unrelated such as the miR-430, miR-302 and miR-467a families (http://www. [score:1]
miR-430 and miR-302 appear in the zebrafish and chick genomes and have therefore been acquired before the split of the mammalian lineage. [score:1]
[1 to 20 of 4 sentences]
30
[+] score: 10
Treatment days miRNAExpression change [#] Predicted mRNA target(s)Expression change [#]GD 8/11 [†] miR-1192 ↑ Atf1, Gng4, Map3k1, Rpe, Setd2, Stxbp6, Zc3h6 ↓ miR-532-5p ↑ Atf1, Itpripl2, Stxbp6 ↓GD 14/16 [*] miR-10b ↓ Aak1 ↑ miR-184 ↓ Myl9 ↑ miR-302c ↑ Ccdc6, Mfap3, Ptpro, Rnd3, Rpl36a/r, Sema3c, Stoml3, Supt3h ↓ miR-342-5p ↓ Aak1, Cables2, Rhog ↑ miR-343 ↑ Asic4, Dcn, Gpr116, Ptpro, Stoml3 ↓ miR-449b ↓ Ina ↑PD 4/7 [†] miR-26b ↑ Adam9, Chsy1, Cnr1, Exoc8, Hs6st1, Lingo1, Map3k7, Mras, Pfkfb3, Ppm1b, Rhou, Sema6d, Shank2, Tab3, Tdrd7, Ube2j1 ↓ miR-34b-5p ↓ Kitl ↑ miR-184 ↑ Ncor2, Prkcb ↓ miR-721 ↑ Akap11, B4galt, Cnr1, Efnb2, Fam20b, Ino80, Irf1, Lrrk2, Ncoa3, Pfkfb3, Ppargc1a, Rbm9, Shank2, Spen, Sphk2, Tsc1, Wdfy3 ↓ miR-1970 ↓ Arhgap6 ↑ # Significance for expression change was 1.2-fold, p < 0.05. [score:9]
Similarly, the miR-302 family of miRNAs involved in cell cycle progression and the maintenance of embryonic stem-cell pluripotency, potentially through its interactions with WNT signaling (Groenendyk and Michalak, 2014). [score:1]
[1 to 20 of 2 sentences]
31
[+] score: 10
Quantitation of p21 protein levels reportedly regulated post-transcriptionally by miRNAs of the hsa-miR-302 family [23] revealed the expected down-regulation of this protein in IGROV-1 cells transfected with hsa-miR-302b precursor (data not shown), suggesting that hsa-miR-302b exerts biological effects in IGROV-1 cells similar to those observed in other cellular mo dels. [score:5]
Moreover, a very recent study reports direct regulation of p21 protein by members of the miR-302 family activated following DNA damage in human embryonic stem cells [20], further suggesting that miR-302 can impact the response to DNA-damaging agents by modulating different target molecules. [score:5]
[1 to 20 of 2 sentences]
32
[+] score: 9
Other miRNAs from this paper: mmu-mir-302a, mmu-mir-302b, mmu-mir-302d
Overexpressed miR-302 cluster or decreased MBD2 expression was thought to increase NANOG gene expression in cells progressing toward complete reprogramming [38]. [score:7]
Lee MR Prasain N Chae HD Kim YJ Mantel C Yoder MC Broxmeyer HE Epigenetic regulation of NANOG by miR-302 cluster-MBD2 completes induced pluripotent stem cell reprogrammingStem Cells. [score:2]
[1 to 20 of 2 sentences]
33
[+] score: 7
Briefly, 1500 ng of biotinylated cRNA was hybridised to Illumina expression BeadChips (Mouse-6 v1.1 for mmu-miR-291-3p and mmu-miR-25 mimics and cell line expression profiles, and Mouse-6 v2 for mmu-miR-302, mmu-miR-292-5p, mmu-miR-106a, mmu-miR-21 and mmu-miR-298 mimics. [score:5]
miRIDIAN Negative Control #2 (Dharmacon CN-002000-01-05) miRIDIAN mmu-miR-291-3p mimic (Dharmacon C-310470-01-0005) miRIDIAN mmu-miR-25 mimic (Dharmacon C-310564-01-0005) miRIDIAN mmu-miR-302 mimic (Dharmacon C-310483-05-0005) miRIDIAN mmu-miR-292-5p mimic (Dharmacon C-310471-03-0005) miRIDIAN mmu-miR-106a mimic (Dharmacon C-310488-07-0005) miRIDIAN mmu-miR-21 mimic (Dharmacon C-310515-05-0005) miRIDIAN mmu-miR-298 mimic (Dharmacon C-310479-07-0005) Trizol purified RNA was cleaned up with an RNeasy MiniElute Cleanup Kit (Qiagen). [score:1]
miRIDIAN Negative Control #2 (Dharmacon CN-002000-01-05) miRIDIAN mmu-miR-291-3p mimic (Dharmacon C-310470-01-0005) miRIDIAN mmu-miR-25 mimic (Dharmacon C-310564-01-0005) miRIDIAN mmu-miR-302 mimic (Dharmacon C-310483-05-0005) miRIDIAN mmu-miR-292-5p mimic (Dharmacon C-310471-03-0005) miRIDIAN mmu-miR-106a mimic (Dharmacon C-310488-07-0005) miRIDIAN mmu-miR-21 mimic (Dharmacon C-310515-05-0005) miRIDIAN mmu-miR-298 mimic (Dharmacon C-310479-07-0005) Trizol purified RNA was cleaned up with an RNeasy MiniElute Cleanup Kit (Qiagen). [score:1]
[1 to 20 of 3 sentences]
34
[+] score: 7
p53 expression is inhibited by miR-125b [2], while p63 is inhibited by miR-302, miR-21, and miR-92 [3], [4], [5]. [score:7]
[1 to 20 of 1 sentences]
35
[+] score: 6
In agreement with the literature [34, 35], members of the miR-302/367 cluster, which are more expressed in EpiSC, and the miR-290/295 cluster, which are more abundant in ES cells, were up- and down-regulated, respectively, at the ES–ELA transition. [score:6]
[1 to 20 of 1 sentences]
36
[+] score: 6
Moreover, alignment of miRs that could regulate the Wnt reporter made intra- and inter -family related functional consensus sequences apparent (i. e. the seed of miR-1 and miR-613 or within the miR-302 and -515 families (Fig. S8)). [score:2]
Alignment to identify a functional consensus in the miR-515 family and its overlap with modulators the miR-302 family in regarding their ability to modulate the Wnt pathway. [score:1]
Moreover, this consensus sequence is also highly shared by the miR-activators of the miR-302 family. [score:1]
Of these, miR-302a and miR-302d are members of the miR-302 family and miR-519e, -519b, and -517a belong to the miR-515 family. [score:1]
Figure S8 Extraction of a consensus sequence of identified miRs within the miR-515 and miR-302 family. [score:1]
[1 to 20 of 5 sentences]
37
[+] score: 6
Instead, the miR-302 cluster was the highest expressed in human and rhesus macaque [14, 30, 31], indicating the functional divergence of stemness miRNA clusters in primate lineages. [score:3]
MiR-290-295 and miR-302 clusters are transcriptionally regulated by Oct-4/Sox2 [29]. [score:2]
The miR-290-295 cluster contains multiple mature miRNAs with seed sequences similar or identical to those in the miR-302 cluster [6]. [score:1]
[1 to 20 of 3 sentences]
38
[+] score: 6
The genes and miRNAs expected to be enriched in iPSCs/ESCs, from the literature [18, 21, 38– 42], include transcription factors involved in maintaining “stemness” (FOXD3, GATA6, NANOG, NR6A1, POU5F1, SOX2, UTF1, TFCP2L1, and ZFP42), signaling molecules involved in pluripotency and self-renewal (CRABP2, EDNRB, FGF4, FGF5, GABRB3, GAL, GRB7, IFITM1, IL6ST, KIT, LEFTY1, LEFTY2, LIFR, NODAL, NOG, NUMB, PTEN, SFRP2, and TDGF1), cytokines and growth factors (FGF4, FGF5, LEFTY1, LEFTY2, NODAL, and TDGF1), other ESC-specific genes (BRIX1, CD9, DIAPH2, DNMT3B, IFITM2, IGF2BP2, LIN28A, PODXL, REST, SEMA3A, TERT, ESRG, and GJA1), and miRNAs (miR-302a, miR-302c, miR-371a, miR-302b, miR-302d, miR-372, miR-373, miR-92a-1, miR-92a-2, miR-92b, miR-17, miR-20a, and miR-18a) that were highly enriched in genes and miRNAs that were expressed (NRC ≥ 20) in our reprogrammed iPSCs and the majority of them showed significant upregulation (FC ≥ 2.0, FDR ≤ 0.05) during iPSC reprogramming (Figure 4(c)). [score:6]
[1 to 20 of 1 sentences]
39
[+] score: 6
Recently, it was discovered that ectopic expression of the miR302/367 cluster, combined with Hdac2 suppression, can directly and efficiently reprogram both mouse and human fibroblasts without supplementation with any of the Yamanaka factors (39). [score:6]
[1 to 20 of 1 sentences]
40
[+] score: 6
In the context of a putative role of miRNA in pGE, it is noteworthy that several mRNAs, upregulated upon mTEC maturation, showed tissue-specific expression patterns, i. e. being restricted to brain (miR-124 and miR-129), heart (miR-499), testis (miR-202), skin (miR-203) or embryo (miR-467 and miR-302). [score:6]
[1 to 20 of 1 sentences]
41
[+] score: 5
Of these, 29, including the miR-302 and -371/372/373 clusters, were associated with pluripotency and uniquely expressed in hESCs. [score:3]
Particularly, the miR-302 cluster (miR-302a, -302a*, -302b, -302b*, -302c, -302c*, -302d, and -302d*) located within intron 8 of LARP7 and the 371/372/373 cluster (miR-371-3p, -371-5p, -372, and -373) located within an intergenic region of chromosome 19 have been previously shown to associate with pluripotency [33]– [35]. [score:1]
The first step requires the loss of pluripotency and embryonic stemness that are mediated by miRs including the miR-302 and -371/372/373 clusters. [score:1]
[1 to 20 of 3 sentences]
42
[+] score: 5
The qPCR (Figure  2B) confirmed strong and mouse ESC-selective expression for both miR-302 and uc. [score:3]
miR-302 was used as a positive control. [score:1]
We used ESC-specific miR-302 as a positive ncRNA control [20, 25]. [score:1]
[1 to 20 of 3 sentences]
43
[+] score: 5
In human embryonic stem cells (ESCs), SOX2 and OCT4 promote the expression of miR-302, a cluster of 8 microRNAs expressed in pluripotent cells, and miR-302a post-transcriptionally represses Ccnd1 [69]. [score:5]
[1 to 20 of 1 sentences]
44
[+] score: 5
Leivonen reported that five ERα -regulating miRNAs (e. g. miR-18a, miR-18b, miR-193b, miR-302c, and miR-206) directly targeted ERα in the 3′UTR [29]. [score:5]
[1 to 20 of 1 sentences]
45
[+] score: 5
Other miRNAs from this paper: mmu-mir-302a, mmu-mir-302b, mmu-mir-302d
To date, only one study has reported sexually dimorphic gene expression in PGCs before their differentiation; the microRNA miR-302 is XY-specifically expressed at 8.5 and 9.5 dpc [66]. [score:5]
[1 to 20 of 1 sentences]
46
[+] score: 5
In several cases NANOG and LIN28 factors were added to the reprogramming cocktail and/or expression of nuclear transcription factors was combined with either addition of small chemical compounds or expression of Simian virus 40 large T antigen (SV40 T), catalytic subunit of human telomerase reverse transcriptase (hTERT), or micro RNA cluster 302/367 (miR-302/367) to achieve higher reprogramming efficiency and stability of iPSC lines. [score:5]
[1 to 20 of 1 sentences]
47
[+] score: 5
Card D. A. Hebbar P. B. Li L. Trotter K. W. Komatsu Y. Mishina Y. Archer T. K. Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells Mol. [score:4]
Wang et al. (2013) [24] transfected epithelial-like cells from human urine with episomal vectors carrying Oct4, Sox2, SV40LT, Klf4 and microRNA cluster MIR302–367 through electroporation, and cultured the transfected cells in presence of five chemicals: CHIR99021, PD0325901, A83-01, thiazovivin and DMH1. [score:1]
[1 to 20 of 2 sentences]
48
[+] score: 5
In type 2 diabetic rats, one of the factors that are responsible for anti-angiogenesis is exosomes released by cardiomyocytes that carry mir302 to the endothelial cells 17 and hence, affect the gene expression in the target cell. [score:5]
[1 to 20 of 1 sentences]
49
[+] score: 5
More recently, iPSCs were successfully generated by lentiviral expression of the miR302/367 cluster or transient transfection of miRNA mimics, miR200c, and clusters of miR302s, and miR369s, without any exogenous transcription factor expression [25], [28]. [score:5]
[1 to 20 of 1 sentences]
50
[+] score: 4
In the peripheral CD3 [+] T lymphocytes of DBA-2/J strain, we found 11 miRNAs (miR-302c, miR-691, miR-712, miR-125a-3p, miR-29b*, miR-30b*, miR-10b, miR-149, miR-141, miR-1897-5p and miR-690) that were up-regulated. [score:4]
[1 to 20 of 1 sentences]
51
[+] score: 4
Rather than replacing one or more transcriptional factors using miRNAs in iPS induction [9]– [11], iPS cells can be generated by using only virus -mediated expression or mature miR-302/367 without the need for any other transcription factors. [score:3]
Recent reports have revealed that iPS cells can be generated more rapidly and efficiently by miR-302/367 without any transcription factors, than by OSKM factors [12], indicating a previously known and important role of miRNAs in iPS reprogramming. [score:1]
[1 to 20 of 2 sentences]
52
[+] score: 4
In studies assessing the role of microRNAs in hESCs, it has been reported that p53 can activate the micro -RNA’s: miR-302a, miR-302b, miR-302c and miR-302d, which can subsequently downregulate the p21 mRNA when p53 is activated [18]. [score:4]
[1 to 20 of 1 sentences]
53
[+] score: 3
The only exception is for H1-hESC, whose results were skewed by the extremely high expression of the miR-302 family members and their pri-miRNA. [score:3]
[1 to 20 of 1 sentences]
54
[+] score: 3
In the developing lip, for instance, both miR-203 and members of the miR-302/367 cluster target different isoforms of p63, of which a deletion leads to cleft lip and palate (Warner et al., 2014). [score:3]
[1 to 20 of 1 sentences]
55
[+] score: 3
miR-302c* - - - - - - ND miR-32 +Over -expression of miR-32 was associated with poor outcome of human kidney cancer [53]. [score:3]
[1 to 20 of 1 sentences]
56
[+] score: 3
For example, miR-302, which we have found to be highly enriched in exosomes, has been shown to regulate neural progenitor proliferation, differentiation timing, and survival during neurulation, and knockout or miR-302 results in early embryonic lethality and open neural tube defects [28]. [score:3]
[1 to 20 of 1 sentences]
57
[+] score: 3
Other miRNAs from this paper: mmu-mir-302a, mmu-mir-302b, mmu-mir-302d
Similarly, the Oct4 and miR302 promoter regions in ES cells have been validated to be under the regulation of JMJD1C -dependent hypomethylation of H3K9 modification to retain their active states of transcription [31, 32]. [score:2]
The pluripotency -associated microRNA miR302 represses the neural differentiation of ES cells, whose transcription is enhanced by the OCT4 and JMJD1C compound [31]. [score:1]
[1 to 20 of 2 sentences]
58
[+] score: 3
Other miRNAs from this paper: mmu-mir-294, mmu-mir-302a, mmu-mir-302b, mmu-mir-302d
2013.07.029 23972987 8. Subramanyam D Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cellsNat. [score:3]
[1 to 20 of 1 sentences]
59
[+] score: 3
For example, the expression of a miR302/367 cluster (comprised of 5 miRNAs) by miR367 activation initiates the process two-fold more effectively than OCT4/SOX2/KLF4/MYC-derived methods and precludes genes breaks or transgene reactivation (Anokye-Danso et al. 2011). [score:3]
[1 to 20 of 1 sentences]
60
[+] score: 3
This is in agreement with the fact that high expression levels of miR-302 cluster are typical of mouse epiblast stem cells [48]. [score:3]
[1 to 20 of 1 sentences]
61
[+] score: 2
Epigenetic regulation of NANOG by miR-302 cluster-MBD2 completes induced pluripotent stem cell reprogramming. [score:2]
[1 to 20 of 1 sentences]
62
[+] score: 2
The development of this miR-302/367 -mediated iPSC (termed mirPSC) may provide tools to deal with the obstacles facing some current iPSC reprogramming methods [41]. [score:2]
[1 to 20 of 1 sentences]
63
[+] score: 2
The maGS cells also expressed higher level of germ cell markers characteristic of primordial germ cells and spermatogonia compared with ES cells [28], although the expression pattern of the ES cell-specific miR-290 and miR-302 cluster of miRNA in maGS cells resembled that of the ES cells [27]. [score:2]
[1 to 20 of 1 sentences]
64
[+] score: 2
The miR-302/367 cluster has been shown to regulate the balance between lung progenitor cell proliferation and differentiation, as well as progenitor cell polarity [60]. [score:2]
[1 to 20 of 1 sentences]
65
[+] score: 2
Eight miRNAs (miR-126-5p, miR-99a, miR-324-5p, miR-762, miR-29a, miR-302c, miR-295, miR-20b) were randomly selected to confirm the microarray results using real-time RT-PCR. [score:1]
To validate the microarray results, eight miRNAs were selected for further experimental confirmation: miR-126-5p, miR-99a, miR-324-5p, miR-762, miR-29a, miR-302c, miR-295, miR-20b. [score:1]
[1 to 20 of 2 sentences]
66
[+] score: 1
Two probes (corresponding to mmu-miR-302c and -370) with extremely large values were deemed to be erroneous signals and excluded prior to embedding. [score:1]
[1 to 20 of 1 sentences]
67
[+] score: 1
173 (miR-186-5p, miR-208a-5p, miR-291a-3p, miR-294-3p, miR-295-3p, miR-302a-3p, miR-302b-3p, miR-302c-3p and miR-302d-3p). [score:1]
[1 to 20 of 1 sentences]
68
[+] score: 1
Another study demonstrated around a 10% efficiency of preparing mouse and human primary iPSCs (i. e. not from iPSC-derived differentiated cells) using the miR302/367 cluster [12]. [score:1]
[1 to 20 of 1 sentences]
69
[+] score: 1
Also, miRNAs can induce somatic cells to pluripotency, as with the miR302/367 cluster [5]. [score:1]
[1 to 20 of 1 sentences]
70
[+] score: 1
The miRNAs chosen include highly conserved and ubiquitous miRNAs (let-7, miR-125) as well as representative tissue-specific miRNAs from stem cells (miR-302), muscle (miR-1), blood (miR-150), and nervous system (miR-9, miR-124, miR-128, miR-132, and miR-138). [score:1]
[1 to 20 of 1 sentences]
71
[+] score: 1
Mathieu et al have shown that hypoxia, through hypoxia-inducible factor (HIF), can induce an hESC-like transcriptional program, including the induced pluripotent stem cell (iPSC) inducers, OCT3/4, Nanog, SOX2, KLF4, c-Myc, and microRNA-302 in several cancer cell lines derived from multiple tissues [18]. [score:1]
[1 to 20 of 1 sentences]
72
[+] score: 1
Other miRNAs from this paper: mmu-mir-302a, mmu-mir-302b, mmu-mir-302d
To develop safer, non-integrative techniques, Anokye-Danso et al. (87) reported the successful reprogramming of mouse and human somatic cells using miR302/367 microRNAs. [score:1]
[1 to 20 of 1 sentences]
73
[+] score: 1
We have a collection of both H1 hESCs as a control and iPSCs derived in our laboratories, mostly from human urine cells (hU) by oriP/EBNA episomal vectors carrying a combination of reprogramming factors Oct4, Sox2, SV40LT, Klf4 and miR302/367 through electroporation [22, 23]. [score:1]
[1 to 20 of 1 sentences]
74
[+] score: 1
miR-373 belongs to the miR-520/-373 family, which consists of three different miRNA clusters (miR-302/-367, miR-371/-372/-373, and miR-520) [27]. [score:1]
[1 to 20 of 1 sentences]
75
[+] score: 1
In addition, Jhdm1b might cooperate with OCT4 for activation of the miR-302/367 miRNA cluster, probably facilitating OCT4 access [164]. [score:1]
[1 to 20 of 1 sentences]
76
[+] score: 1
miR-302 is required for timing of neural differentiation, neural tube closure, and embryonic viability. [score:1]
[1 to 20 of 1 sentences]
77
[+] score: 1
A previous screening -based study, which examined the effect of 461 individually re-introduced miRNAs on the proliferation of DGCR8 -null cells showed that the defective proliferation was rescued by 14 different miRNAs, including miR-290, miR-302 and the miR-17-92 cluster (40 and refs therein). [score:1]
[1 to 20 of 1 sentences]
78
[+] score: 1
Other miRNAs from this paper: hsa-let-7f-1, hsa-let-7f-2, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-32, mmu-mir-1a-1, mmu-mir-133a-1, mmu-mir-134, mmu-mir-135a-1, mmu-mir-144, mmu-mir-181a-2, mmu-mir-24-1, mmu-mir-200b, mmu-mir-206, hsa-mir-208a, mmu-mir-122, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-181a-1, hsa-mir-214, hsa-mir-200b, mmu-mir-299a, mmu-mir-302a, hsa-mir-1-2, hsa-mir-122, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-144, hsa-mir-134, hsa-mir-206, mmu-mir-200a, mmu-mir-208a, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-24-2, mmu-mir-328, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-214, mmu-mir-135a-2, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-200a, hsa-mir-302a, hsa-mir-299, hsa-mir-361, mmu-mir-361, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, hsa-mir-377, mmu-mir-377, hsa-mir-328, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, hsa-mir-20b, hsa-mir-429, mmu-mir-429, hsa-mir-483, hsa-mir-486-1, hsa-mir-181d, mmu-mir-483, mmu-mir-486a, mmu-mir-367, mmu-mir-20b, hsa-mir-568, hsa-mir-656, mmu-mir-302b, mmu-mir-302d, mmu-mir-744, mmu-mir-181d, mmu-mir-568, hsa-mir-892a, hsa-mir-892b, mmu-mir-208b, hsa-mir-744, hsa-mir-208b, mmu-mir-1b, hsa-mir-302e, hsa-mir-302f, hsa-mir-1307, eca-mir-208a, eca-mir-208b, eca-mir-200a, eca-mir-200b, eca-mir-302a, eca-mir-302b, eca-mir-302c, eca-mir-302d, eca-mir-367, eca-mir-429, eca-mir-328, eca-mir-214, eca-mir-200c, eca-mir-24-1, eca-mir-1-1, eca-mir-122, eca-mir-133a, eca-mir-144, eca-mir-25, eca-mir-135a, eca-mir-568, eca-mir-133b, eca-mir-206-2, eca-mir-1-2, eca-let-7f, eca-mir-24-2, eca-mir-134, eca-mir-299, eca-mir-377, eca-mir-656, eca-mir-181a, eca-mir-181b, eca-mir-32, eca-mir-486, eca-mir-181a-2, eca-mir-20b, eca-mir-361, mmu-mir-486b, mmu-mir-299b, hsa-mir-892c, hsa-mir-486-2, eca-mir-9021, eca-mir-1307, eca-mir-744, eca-mir-483, eca-mir-1379, eca-mir-7177b, eca-mir-8908j
For instance, miR-208, miR-302 (a-d), miR-367 were not detected (at >10 cpm on average) in the heart tissue; miR-134 and miR-208a were not detected in skeletal muscles; miR-483 in liver; or miR-483 and miR-377 in bone [36]. [score:1]
[1 to 20 of 1 sentences]