ESCs and NPCs are two setm cell types which rely on expression of the transcription factor Sox2. We profilled gene expression in ESCs and NPCs to correlate genome-wide Sox2 ChIP-Seq data in these cells with expression of putative targets
SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state.
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View SamplesExpression profiles generated during dissection of the molecular mechanisms underlying direct reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells, iPS).
Dissecting direct reprogramming through integrative genomic analysis.
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View SamplesMicroRNAs (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.
A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
Specimen part
View SamplesAnalysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
Specimen part
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