Role of miRNAs in the neurogenesis of human neural stem cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30572 | GEO | 2012/03/01
SECONDARY ACCESSION(S): PRJNA143367
REPOSITORIES: GEO
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Project description:by use of the model of human embryonic stem cell (hESC)-derived neurogenesis, miRNAs involved in the differentiation from neural stem cells (hNSC) to neurons were profiled and identified. HNSC were differentiated into the neural lineage, out of which the neuronal subset was enriched through cell sorting based on select combinatorial biomarkers: CD15-/CD29Low/CD24High. This relatively pure and viable subpopulation expressed the neuronal marker alpha III-tubulin. The miRNA array demonstrated that a number of miRNAs were simultaneously induced or suppressed in neurons, as compared to hNSC. Real-time PCR further validated the decrease in levels of miR214, but increase in brain-specific miR7 and miR9 in the derived neurons. This experiment includes a total of 6 samples which are divided in to 2 groups, each with 3 biological repeats: 3 untreated normal samples as controls and 3 differentiated samples as the treated condition
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Project description:Dynamic DNA methylation controls gene-regulatory networks underlying cell fate specification. How DNA methylation patterns change during adult hippocampal neurogenesis and their relevance for the generation of new neurons from adult neural stem cells has, however, remained unknown. Here, we show that neurogenesis-associated de novo DNA methylation is critical for maturation and functional integration of adult-born hippocampal neurons. Cell stage-specific bisulfite sequencing revealed a pronounced gain of DNA methylation at neuronal enhancers, gene bodies and binding sites of pro-neuronal transcription factors during adult neurogenesis, which mostly correlated with transcriptional up-regulation of the associated loci. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells specifically impaired dendritic outgrowth and synaptogenesis of new neurons, resulting in impaired hippocampal excitability and specific deficits in hippocampus-dependent learning and memory. Our results highlight that, during adult neurogenesis, remodeling of neuronal methylomes is fundamental for proper hippocampal function.
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