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CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE155218 | GEO | 2020/09/16

REPOSITORIES: GEO

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CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation.

Project description:The chromatin remodeler CHD8 is among the most frequently mutated genes in autism spectrum disorder (ASD). CHD8 has a dosage-sensitive role in ASD, but when and how it becomes critical to human social function is unclear. Here, we conducted genomic analyses of heterozygous and homozygous Chd8 mouse embryonic stem cells and differentiated neural progenitors. We identify dosage-sensitive CHD8 transcriptional targets, sites of regulated accessibility, and an unexpected cooperation with SOX transcription factors. Collectively, our findings reveal that CHD8 negatively regulates expression of neuronal genes to maintain pluripotency and also during differentiation. Thus, CHD8 is essential for both the maintenance of pluripotency and neural differentiation, providing mechanistic insight into its function with potential implications for ASD.

| S-EPMC7486765 | biostudies-literature

CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [RNA-seq]

Project description:The chromatin remodeler CHD8 is among the most frequently mutated genes in autism spectrum disorder (ASD). CHD8 has a dosage-sensitive role in ASD but when and how it becomes critical to human social function is unclear. Here, we conducted genomic analyses of heterozygous and homozygous Chd8 mouse embryonic stem cells and differentiated neural progenitors. We identify dosage-sensitive CHD8 transcriptional targets, sites of regulated accessibility, and an unexpected cooperation with SOX transcription factors. Collectively, our findings reveal that CHD8 negatively regulates expression of neuronal genes to maintain pluripotency and also during differentiation. Thus, CHD8 is essential for both the maintenance of pluripotency and neural differentiation, providing mechanistic insight into its function with potential implications for ASD.

2020-09-16 | GSE155217 | GEO

CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [ChIP-seq]

2020-09-16 | GSE155216 | GEO

CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [ATAC-seq]

2020-09-16 | GSE155215 | GEO

CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation

Project description:CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation

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CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [RNA-seq]

Project description:CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [RNA-seq]

| PRJNA648981 | ENA

CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [ATAC-seq]

Project description:CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [ATAC-seq]

| PRJNA648979 | ENA

CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [ChIP-seq]

Project description:CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [ChIP-seq]

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Transcription factor SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating the neurogenic gene Hes5.

Project description:SOX2 and SOX15 are Sox family transcription factors enriched in embryonic stem cells (ESCs). The role of SOX2 in activating gene expression programs essential for stem cell self-renewal and acquisition of pluripotency during somatic cell reprogramming is well-documented. However, the contribution of SOX15 to these processes is unclear and often presumed redundant with SOX2 largely because overexpression of SOX15 can partially restore self-renewal in SOX2-deficient ESCs. Here, we show that SOX15 contributes to stem cell maintenance by cooperating with ESC-enriched transcriptional coactivators to ensure optimal expression of pluripotency-associated genes. We demonstrate that SOX15 depletion compromises reprogramming of fibroblasts to pluripotency which cannot be compensated by SOX2. Ectopic expression of SOX15 promotes the reversion of a postimplantation, epiblast stem cell state back to a preimplantation, ESC-like identity even though SOX2 is expressed in both cell states. We also uncover a role of SOX15 in lineage specification, by showing that loss of SOX15 leads to defects in commitment of ESCs to neural fates. SOX15 promotes neural differentiation by binding to and activating a previously uncharacterized distal enhancer of a key neurogenic regulator, Hes5. Together, these findings identify a multifaceted role of SOX15 in induction and maintenance of pluripotency and neural differentiation.

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CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-10-07 | E-GEOD-61492 | biostudies-arrayexpress