Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA143687 | ENA |
REPOSITORIES: ENA
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Project description:MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells (mESCs). Examination of a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, revealed strong enrichment for apoptotic regulators, two of which we validated directly: Caspase 2, the most highly conserved mammalian caspase, and Ei24, a p53 transcriptional target. Consistent with these predictions, mESCs lacking miRNAs were more likely to initiate apoptosis following genotoxic exposure to gamma irradiation or doxorubicin. Knockdown of either candidate partially rescued this pro-apoptotic phenotype, as did transfection of members of the mir-290-295 cluster. These findings were recapitulated in a specific mir-290-295 deletion line, confirming that they reflect miRNA functions at physiological levels. In contrast to the basal regulatory roles previously identified, the pro-survival phenotype shown here may be most relevant to stressful gestations, where pro-oxidant metabolic states induce DNA damage. Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target. Three replicates of mouse embryonic stem cells with Dicer (CTRL) compared to three replicates of mouse embryonic stem cells lacking Dicer (CRE)
2011-06-18 | E-GEOD-30012 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells (mESCs). Examination of a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, revealed strong enrichment for apoptotic regulators, two of which we validated directly: Caspase 2, the most highly conserved mammalian caspase, and Ei24, a p53 transcriptional target. Consistent with these predictions, mESCs lacking miRNAs were more likely to initiate apoptosis following genotoxic exposure to gamma irradiation or doxorubicin. Knockdown of either candidate partially rescued this pro-apoptotic phenotype, as did transfection of members of the mir-290-295 cluster. These findings were recapitulated in a specific mir-290-295 deletion line, confirming that they reflect miRNA functions at physiological levels. In contrast to the basal regulatory roles previously identified, the pro-survival phenotype shown here may be most relevant to stressful gestations, where pro-oxidant metabolic states induce DNA damage. Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target.
2011-06-18 | GSE30012 | GEO
Project description:In order to identify direct microRNA targets in mouse embryonic stem cells (mESCs), we generated miR-290-295 KO mutant cell lines, assessed their transcriptomes. We identified novel transcription factors (TF) as potential direct and functional targets of miR-290-295. To assess the role of these TFs, we rescued their expression in the miR-290-295 KO cell line using siPOOLs and profiled their transcriptomes.
2022-07-15 | GSE179451 | GEO
Project description:In order to identify direct microRNA targets in mouse embryonic stem cells (mESCs), we knocked out microRNA effector genes, profiled their transcriptomes and integrated the data with additional published OMICs data sets. To validate the analysis, we generated miR-290-295 KO mutant cell lines, assessed the transcriptome profile and compared the observed misregulation to the predictions of the analysis. We identified the transcription factor Tfap4 as novel potential direct and functional target of miR-290-295. To assess the role of Tfap4, we rescued its expression in the miR-290-295 KO cell line using siPOOLs and profiled the transcriptome.
2022-07-15 | GSE181393 | GEO
Project description:We have analyzed the transcript expression levels in Dicer knock-out embryonic stem (ES) cells 24 hours after transfection with either control siRNA agains Renilla luciferase or miRNA Mimics (Dharmacon) of mmu-miR-290 cluster members in order to identify primary targets of miR-290 cluster miRNAs. Experiment Overall Design: Cell were analysed 24h after transfections in an undifferentiated state. Triplicates of both transfections were analyzed.
2008-06-16 | E-GEOD-8503 | biostudies-arrayexpress
Project description:We have analyzed the transcript expression levels in Dicer knock-out embryonic stem (ES) cells 24 hours after transfection with either control siRNA agains Renilla luciferase or miRNA Mimics (Dharmacon) of mmu-miR-290 cluster members in order to identify primary targets of miR-290 cluster miRNAs. Keywords: Comparison of effect of two different transfections on transcriptome of Dicer-KO ES cells
2008-01-01 | GSE8503 | GEO
Project description:In order to identify direct microRNA targets in mouse embryonic stem cells (mESCs), we knocked out microRNA effector genes, profiled their transcriptomes and integrated the data with additional published OMICs data sets. To validate the analysis, we generated miR-290-295 KO mutant cell lines, assessed the transcriptome profile and compared the observed misregulation to the predictions of the analysis.
2022-07-15 | GSE179450 | GEO
Project description:The miR-290 and miR-302 clusters of microRNAs are highly expressed in naïve and primed pluripotent stem cells, respectively. Ectopic expression of the embryonic stem cell-specific cell cycle regulating (ESCC) family of microRNAs arising from these two clusters dramatically enhances the reprogramming of both mouse and human somatic cells to induced pluripotency. Here, we used genetic knockouts to dissect the requirement for the miR-290 and miR-302 clusters during the reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPSCs) with retrovirally introduced Oct4, Sox2, and Klf4. Knockout of either cluster alone did not negatively impact the efficiency of reprogramming. Resulting cells appeared identical to their embryonic stem cell counterparts. Notably miR-290 knockout cells showed a compensatory increase in miR-302 expression and the combined loss of both clusters blocked the formation of iPSCs. While rare double knockout clones could be isolated, they showed a dramatically reduced proliferation rate, a persistent inability to fully silence the exogenously introduced pluripotency factors, and a transcriptome distinct from individual miR-290 or miR-302 mutant ESC and iPSCs. Taken together, our data show that miR-290 and miR-302 are essential yet interchangeable in reprograming to the induced pluripotent state.
2025-01-10 | GSE268461 | GEO
Project description:A family of vertebrate-specific microRNAs called the ESCC microRNAs regulates proliferation and differentiation of embryonic stem cells. The ESCC microRNAs arise from two genetic loci in mammals, the miR-290/miR-371 and miR-302 loci. While the miR-302 locus is found broadly among vertebrates, the miR-290/miR-371 locus is unique to eutherian species, suggesting a role in placental development. Here, we evaluate that role. A knockin reporter for the mouse miR-290 gene is expressed throughout the embryo until gastrulation, at which time it becomes specifically expressed in extraembryonic tissues and the germline. In the placenta, expression is limited to the trophoblast lineage, where it remains highly expressed until birth. Deletion of the miR-290 gene results in reduced trophoblast progenitor cell proliferation and a reduced DNA content in endoreduplicating trophoblast giant cells. A reduction in placental size precedes a reduction in fetal size and prenatal death of most knockout embryos. The vascular labyrinth shows disorganization with thickening of the barrier between maternal and fetal blood associated with reduced diffusion of a radioactive tracer. Multiple mRNA targets of the cluster miRNAs are upregulated. Together, these data uncover a critical function for the miR-290 in the regulation of a network of genes required for normal placental development, suggesting a central role for this microRNA cluster in the evolution of eutherian species.
2017-03-04 | GSE95687 | GEO
Project description:Transcriptome of miR-290-295 KO mESCs
| PRJNA743870 | ENA