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Analysis of FOXO3 human targets in Huntington's disease neural stem cells

ABSTRACT: Analysis of FOXO3 human targets in Huntington's disease neural stem cells

PROVIDER: PRJNA432220 | ENA |

REPOSITORIES: ENA

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Analysis of FOXO3 human targets in Huntington's disease neural stem cells: FOXO3 nuclear induction [ChIP-Seq]

Project description:We report the identification of F0X03 targets in human Huntington's disease neural stem cells. To this end, we generated FOXO3 ChIP-seq data upon FOXO3 nuclear induction in human Huntington's disease (HD) and CAG-corrected (C116) neural stem cells.

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Analysis of FOXO3 human targets in Huntington's disease neural stem cells: FOXO3 nuclear induction [RNA-Seq]

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Analysis of FOXO3 human targets in Huntington's disease neural stem cells: FOXO3 knock-down [RNA-seq2]

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Analysis of FOXO3 human targets in Huntington's disease neural stem cells: FOXO3 nuclear induction [ChIP-Seq]

Project description:Analysis of FOXO3 human targets in Huntington's disease neural stem cells: FOXO3 nuclear induction [ChIP-Seq]

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FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis

Project description:FOXO transcription factors are central regulators of longevity from worms to humans. FOXO3 – the FOXO isoform associated with exceptional human longevity – preserves adult neural stem cell pools. Here we identify FOXO3 direct targets genome-wide in primary cultures of adult neural progenitor cells (NPCs). Interestingly, FOXO3-bound sites are enriched for motifs for bHLH transcription factors and FOXO3 shares common targets with the pro-neuronal bHLH transcription factor ASCL1/MASH1 in NPCs. Analysis of the chromatin landscape reveals that FOXO3 and ASCL1 are particularly enriched at the enhancers of genes involved in neurogenic pathways. Intriguingly, FOXO3 inhibits ASCL1-dependent neurogenesis in NPCs and direct neuronal conversion in fibroblasts. FOXO3 also restrains neurogenesis in vivo. Our study identifies a genome-wide interaction between the pro-longevity transcription factor FOXO3 and the cell fate determinant ASCL1, and raises the possibility that FOXO3’s ability to restrain ASCL1-dependent neurogenesis may help preserve the neural stem cell pool. ChIP-seq profiles of two transcription factors (FOXO3 and ASCL1) and three histone marks (H3K4me1, H3K4me3 and H3K27me3) in adult mouse neural progenitor cells.

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FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis

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Role of FoxO3 in adult neural stem cell maintenance in mice

Project description:In the nervous system, neural stem cells (NSC) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3-/- mice have fewer NSC in vivo than wild type counterparts. NSC isolated from adult FoxO3-/- mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSC suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSC might have important implications for counteracting brain aging in long-lived species.

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Analysis of FOXO3 human targets in Huntington's disease neural stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

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