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Identifying ASCL1 target genes in primary GBM stem cell cultures [ChIP-seq]

ABSTRACT: ASCL1 mediates neuronal differentiation of GBM stem cell (GSC) cultures. We sought to identify genomic targets of ASCL1 in primary human GSC cultures. In this dataset, we include ChIP-seq data obtained from GSC cultures harbouring a CRISPR-deletion of ASCL1. We assessed differential ASCL1 binding between control and GSC cultures induced to overexpress ASCL1 after 18 hours of doxycycline treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87618 | GEO | 2017/07/13

SECONDARY ACCESSION(S): PRJNA345388

REPOSITORIES: GEO

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Identifying ASCL1 target genes in primary GBM stem cell cultures [RNA-seq]

Project description:ASCL1 mediates neuronal differentiation of GBM stem cell (GSC) cultures. We sought to identify targets of ASCL1 in primary human GSC cultures. In this dataset, we include RNA-seq data obtained from GSC cultures harbouring a CRISPR-deletion of ASCL1. We assessed differential gene expression between control and GSC cultures induced to overexpress ASCL1 after 7 days of doxycycline treatment.

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ChIP NS5 Ascl1-ERT2

Project description:Here we performed a ChIP-seq experiment on a sample of adherent cultures of mouse neural stem cells (NS5 cell line) under normal growth conditions and upon short term activation (30 minutes) of an inducible version of the proneural factor Mash1/Ascl1 (Ascl1-ERT2). This resulted in the generation of a genome-wide map of Ascl1 binding to chromatin.

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Project description:As a proneural gene, ASCL1 was reported to be important to neurogenesis. To better illustrate the role of ASCL1 in human telencephalon development, we genetically engineered an ASCL1 knockout (KO) hESC line and ASCL1 rescue (RE) hESC line, and then preformed RNA sequencing when WT, KO and RE were differentiated into neural progenitors in vitro. Our results showed that ASCL1 KO hESCs could be regularly maintained in vitro, and could be efficiently specified into neuroectoderm cells and following telencephalic neural progenitors. Remarkably, dorsal progenitors-derived from ASCL1 KO hESCs failed to differentiate into DCX positive neuroblasts. In addition, dorsal and ventral progenitors retained higher expression of VZ/ESVZ genes but had much lower expression of LSVZ genes after KO of ASCL1. Re-introducing of ASCL1 in KO hESCs through a doxycycline (Dox) inducible overexpression system reversed the gene expression changes induced by cortical progenitors with ASCL1 KO. Taken all these together, our results revealed a pivotal role of ASCL1 in both dorsal and ventral telencephalic development by progressing the cycling progenitors within the ESVZ to post-mitotic early born neurons in the LSVZ in human telencephalon.

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