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Epigenome profiling and editing of neural progenitor cells in the developing mouse neocortex

ABSTRACT: Epigenome profiling and editing of neural progenitor cells in the developing mouse neocortex

PROVIDER: PRJNA355401 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5045903.fastq.gz	Fastqsanger.gz
	SRR5045904.fastq.gz	Fastqsanger.gz
	SRR5045905.fastq.gz	Fastqsanger.gz
	SRR5045906.fastq.gz	Fastqsanger.gz
	SRR5045907.fastq.gz	Fastqsanger.gz

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Epigenome profiling and editing of neural progenitor cells in the developing mouse neocortex [ChIP-seq]

Project description:The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here we present genome-wide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs available for future exploration. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator Eomes. We used catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the Eomes locus in vivo, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.

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Primate-expressed EPIREGULIN promotes basal progenitor proliferation in the developing neocortex

Project description:Neocortex expansion during evolution is linked to higher numbers of neurons thought to result from increased proliferative capacity and neurogenic potential of basal progenitors during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of both major basal progenitor types, intermediate basal progenitors and basal radial glia, whereas ablation of EPIREGULIN in human cortical organoids reduces basal progenitor proliferation. Here, we analyzed gene expression changes upon addition of EPIREGULIN to the mouse neocortex for 24 hours using hemisphere rotation culture. We performed fluorescent activated cell sorting to isolate radial glia (RG), intermediate progenitor (IP) cells and neurons (N) based on the nuclear markers Sox2 and Tbr2, and expression of GFP in neurons isolated from a Tubb3::GFP mouse reporter line.

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Epigenome profiling and editing of neural progenitor cells in the developing mouse neocortex

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

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