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

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

PROVIDER: PRJNA648982 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12332810.fastq.gz	Fastqsanger.gz
	SRR12332811.fastq.gz	Fastqsanger.gz
	SRR12332812.fastq.gz	Fastqsanger.gz
	SRR12332813.fastq.gz	Fastqsanger.gz

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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.

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

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

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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 [ATAC-seq]

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

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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]

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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 safeguards early neuroectoderm differentiation in human ESCs and protects from apoptosis during neurogenesis

Project description:To understand the function of CHD8 in human ESC and neural differentiation, we generated the CHD8 knockout human ESCs and characterize the effect of loss-of-function of CHD8 on pluripotency maintenance and neuroectoderm determination by utilizing an efficient neuroectoderm differentiation protocol. Samples from hESC, CHD8KO_hESC and their derived-neural progenitor cells (hNPC) were collected for high-throughput sequencing with at least two replicates for each sample. Differentially expressed genes analysis showed loss of CHD8 affect the genes in ESC and NPC.

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CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation

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

2020-09-16 | GSE155218 | GEO

Transcriptome of iPSC-derived Neural Cells with Heterozygous Knockout in CHD8

Project description:CHD8, encoding Chromodomain helicase DNA binding protein 8, is a top autism spectrum disorders (ASDs) risk gene. To better understanding the molecular links between CHD8 functions and ASD, we have applied the CRISPR/Cas9 technology to knockout one copy of CHD8 in induced pluripotent stem cells (iPSCs) to mimic the loss of function status that would exist in the developing human embryo prior to neuronal differentiation. Transcriptome profiling (RNA-seq) in neural progenitors and early differentiating neurons revealed that CHD8 hemizygosity (CHD8+/-) affected the expression of several thousands of genes, enriched for functions of neural development, Î²-catenin/Wnt signaling, extracellular matrix, and skeletal system development. Moreover, CHD8 regulates multiple genes implicated in ASD, schizophrenia and genes associated with brain volume. iPSCs derived from a healthy subject were transduced with CRISPR/Cas9 vectors with single guide RNA sequences to target the N-terminal of CHD8 protein to generate truncated mutation seach of the two target sequences. Two clones, one with a 2-bp (KO1) and the other with a 10-bp (KO2) heterozygous deletion were found.The CHD8+/- iPSC lines were used to generate NPCs and early differentiating neurons for RNA-seq analysis, together with samples prepared from the parental clones, for a total of 8 samples (two biological replicates of wild-type (WT) and CHD8+/- at two neurodevelopmental stages).

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