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Molecular basis of BMP-responsiveness switching during neural development

ABSTRACT: Bone morphogenetic proteins induce neuronal and astrocytic differentiation in mid-gestational (e.g. E11+2DIV), and late-gestational (e.g. E14+5DIV) neural stem cells (NSCs), respectively. We found that Smads, downstream transcription factors of BMP signaling, target dramatically different genomic regions in the neurogenic and gliogenic NSCs. The purpose of this study is to understand histone H3K27 tri-methylation profiles around Smads-binding sites in neurogenic and gliogenic NSCs, and uncover the mechanisms underlying distinct effects of BMPs on developmentally different NSCs. We found that histone H3K27 tri-methylation around Smads binding sites quickly change as gestation proceeds, strongly associated with the alteration of accessibility of Smads to the regions.

ORGANISM(S): Mus musculus

PROVIDER: GSE174306 | GEO | 2021/11/16

REPOSITORIES: GEO

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Analysis of Mll1-deficiency identifies neurogenic transcriptional modules and Brn4 as a factor for direct astrocyte-to-neuron reprogramming

Project description:BACKGROUND: Mixed lineage leukemia-1 (Mll1) epigenetically regulates gene expression patterns that specify cellular identity in both embryonic development and adult stem cell populations. In the adult mouse brain, multipotent neural stem cells (NSCs) in the subventricular zone (SVZ) generate new neurons throughout life and Mll1 is required for this postnatal neurogenesis but not for glial cell differentiation. Analysis of Mll1-dependent transcription may identify neurogenic genes useful for the direct reprogramming of astrocytes into neurons. OBJECTIVE: To identify Mll1-dependent transcriptional modules and determine whether genes in the neurogenic modules can be used to directly reprogram astrocytes into neurons. METHODS: We performed gene coexpression module analysis on microarray data from differentiating wild-type and Mll1-deleted SVZ NSCs. Key developmental regulators belonging to the neurogenic modules were overexpressed in Mll1-deleted cells and cultured cortical astrocytes, and cell phenotypes were analyzed by immunocytochemistry and electrophysiology. RESULTS: Transcriptional modules that correspond to neurogenesis were identified in wild-type NSCs. Modules related to astrocytes and oligodendrocytes were enriched in Mll1-deleted NSCs, consistent with their gliogenic potential. Overexpression of genes selected from the neurogenic modules enhanced the production of neurons from Mll1- deleted cells, and the overexpression of Brn4 (Pou3f4) in non-neurogenic cortical astroglia induced their transdifferentiation into electrophysiologically active neurons. CONCLUSIONS: Our results demonstrate that Mll1 is required for the expression of neurogenic - but not gliogenic - transcriptional modules in a multipotent NSC population and further indicate that specific Mll1-dependent genes may be useful for direct reprogramming strategies.

2016-03-06 | GSE56835 | GEO

Single cell RNA-seq analysis of feeder-free iPSC-derived gliogenic NS/PCs and neurogenic NS/PCs

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Comprehensive proteome of the adult neural stem cell niche identifies key regulators of adult neurogenesis

Project description:Neural stem cells (NSCs) generating new neurons are restricted to few niches in the adult mammalian brain, while the remainder rather promotes gliogenesis. Here we take advantage of the spatial separation of an NSC niche (the subependymal zone) and the region to where the newly generated neurons migrate and integrate (the olfactory bulb). Using state-of-the-art mass spectrometry we present a comprehensive proteomic characterization of these niches compared to a region of the normal brain parenchyma (cerebral cortex) that is not contusive to neurogenesis and new neuron integration. We find unique compositions of regulatory ECM components in the neurogenic niche, with quiescent NSCs as a main source of their local ECM, including the multi-functional enzyme transglutaminase 2 that we identify as crucial for neurogenesis. Atomic force microscopy further corroborates indications from the proteome that neurogenic niches are significantly stiffer than the non-neurogenic parenchyma, highlighting the unique properties of these special niches.

2020-01-27 | PXD016632 | Pride

Post-transcriptional control of a stemness signature by RNA-binding 8 protein MEX3A regulates adult neurogenesis

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2023-01-08 | PXD038983 | Pride

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2011-12-31 | E-GEOD-21208 | biostudies-arrayexpress

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2008-06-18 | E-GEOD-8034 | biostudies-arrayexpress

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2019-10-24 | E-MTAB-8363 | biostudies-arrayexpress

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2019-10-24 | E-MTAB-8379 | biostudies-arrayexpress

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