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Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex

ABSTRACT: Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex

PROVIDER: PRJNA850446 | ENA |

REPOSITORIES: ENA

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Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex [ChIP-seq]

Project description:Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex [ChIP-seq]

| PRJNA850450 | ENA

Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex [RNA-seq]

Project description:Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex [RNA-seq]

| PRJNA850451 | ENA

Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex

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

2022-12-31 | GSE206408 | GEO

Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex [ChIP-seq]

Project description:To identify whether DHFR deficiency affects neurogenesis by modulating H3K4me3 methylation marks.

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Dihydrofolate reductase metabolic activity controls neurogenic transitions in the developing human and mouse neocortex [RNA-seq]

Project description:To identify how DHFR deficiency affects neurogenesis by modulating neocortical gene expression at E12.5.

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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.

2024-02-19 | GSE228007 | GEO

Extracellular matrix-inducing Sox9 orchestrates basal progenitor proliferation and gliogenesis in developing neocortex

Project description:Neocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. Examination of Sox9 expression reveals that Sox9 is expressed in BPs of developing ferret and human, but not mouse neocortex. Functional studies by conditional Sox9 expression in the mouse BP lineage demonstrate increased BP proliferation, reduced Tbr2 and induction of Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell non-autonomous stimulation of BP proliferation followed by increased production of upper-layer neurons. Collectively, our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic as well as gliogenic BP cell fate, suggesting that Sox9 acts a master regulator in the subventricular zone to promote neocortical expansion.

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Progenitor cell diversity in the developing mouse neocortex

Project description:In the mammalian neocortex, diverse projection neuron types are generated by the same pool of neural progenitors in sequential waves. How neuronal cell type specification is related to developmental timing remains unclear. To determine whether neural progenitor cell heterogenity correlates with neuronal type spcification, we performed single cell RNA sequencing analysis of the developing mouse neocortex (E10.5 through E18.5) by Drop-Seq. We uncovered cellular and molecular diversity among neuroepithelial cells, radial glial cells, intermediate progenitors and neuron types.

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Project description:A specific subpopulation of neural progenitor cells, the basal radial glia cells (bRGCs) of the outer subventricular zone (OSVZ), are thought to have a key role in the evolutionary expansion of mammalian neocortex. In the developing lissencephalic mouse neocortex, bRGCs exist at low abundance and show significant molecular differences from bRGCs in developing gyrencephalic species. Here, we demonstrate that developing mouse medial neocortex, in contrast to the canonically studied lateral neocortex, exhibits an OSVZ and an abundance of bRGCs similar to that in developing gyrencephalic neocortex. Unlike bRGCs in developing mouse lateral neocortex, the bRGCs in medial neocortex exhibit human bRGC-like gene expression, including expression of Hopx, a human bRGC marker. Disruption of Hopx expression in mouse embryonic medial neocortex and forced Hopx expression in mouse embryonic lateral neocortex demonstrate that Hopx is required and sufficient, respectively, for a bRGC abundance as found in developing gyrencephalic neocortex. Taken together, our data identify a novel bRGC subpopulation in developing mouse medial neocortex that is highly related to bRGCs of developing gyrencephalic neocortex.

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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.

2017-08-03 | GSE90447 | GEO

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