Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Changing and stable chromatin accessibility supports transcriptional overhaul during neural stem cell activation

ABSTRACT: Adult neural stem cells are largely quiescent, and require transcriptional reprogramming to re-enter the cell cycle before neurogenesis. However, mechanisms underlying the transcriptional overhaul during NSC activation remain undefined. Here, we identify the chromatin accessibility differences between primary neural stem/progenitor cells in quiescent and activated states. These distinct cellular states exhibit shared and unique chromatin profiles, both associated with gene regulation. Interestingly, accessible chromatin states specific to activation or quiescence are active enhancers bound by pro-neurogenic and quiescence factors, ASCL1 and NFI. In contrast, shared sites are enriched for core promoter elements associated with translation and metabolism. Unexpectedly, through integrated analysis, we find that many sites that become accessible during NSC activation are linked to downregulation of gene expression and associated with pro-quiescence factors, revealing a novel mechanism that may preserve quiescence re-entry. Together, our findings reveal how accessible chromatin states regulate the transcriptional switch between NSC quiescence and activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE161578 | GEO | 2021/11/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells

Project description:Adult neural stem cells (NSCs) must tightly regulate quiescence and proliferation. Single cell analysis has suggested a continuum of cell states as NSCs exit quiescence. Here we capture and characterize in vitro primed quiescent NSCs and identify LRIG1 as an important regulator. We show that BMP-4 signaling induces a dormant non-cycling quiescent state (d-qNSCs), whereas combined BMP-4/FGF-2 signalling induces a distinct primed quiescent state poised for cell cycle re-entry. Primed quiescent NSCs (p-qNSCs) are defined by high levels of LRIG1 and CD9, as well as an interferon response signature, and can efficiently engraft into the adult subventricular zone (SVZ) niche. Genetic disruption of Lrig1 in vivo within the SVZ NSCs leads an enhanced proliferation. Mechanistically, LRIG1 primes quiescent NSCs for cell cycle re-entry and EGFR responsiveness by enabling EGFR protein levels to increase but limiting signaling activation. LRIG1 is therefore an important functional regulator of NSC exit from quiescence.

2021-03-18 | GSE168189 | GEO

SEZ cells populations

Project description:Characterization of neural stem cells (NSC) from the adult rodent subependymal niche by flow cytometry and traceable nucleoside retention assays have indicated the co-existence of activated and quiescent NSC in this niche. Single-cell deep-sequencing has further revealed different NSC molecular states with regards to cell-cycle gene expression: quiescent, primed for activation, and fully activated. Here, we provide a multi-level procedure to classify all cells of the subependymal niche, without the need for reporter mice, into populations with coherent transcriptomes that can be functionally assayed. Our strategy reveals that primed NSC are slowly proliferating cells that contribute to NSC cultures and that neurospheres contain NSC which retain a primed-like molecular signature and exhibit slow cycling and long-term self-renewal. Our strategy provides a way to functionally assay NSC heterogeneity and to study quiescence levels in NSC populations.

2020-11-22 | GSE138243 | GEO

Autofluorescence is a biomarker of neural stem cell activation state [Subventricular zone]

Project description:Neural stem cells (NSCs) in the adult brain are primarily quiescent but can activate and enter the cell cycle to produce newborn neurons. NSC quiescence can be regulated by disease, injury, and age, however our understanding of NSC quiescence is limited by technical limitations imposed by the bias of markers used to isolate each population of NSCs and the lack of live-cell labeling strategies. Fluorescence lifetime imaging (FLIM) of autofluorescent metabolic cofactors has previously been used in other cell types to study shifts in cell states driven by metabolic remodeling that change the optical properties of these endogenous fluorophores. Here we asked whether autofluorescence could be used to discriminate NSC activation state. We found that quiescent NSCs (qNSCs) and activated NSCs (aNSCs) each have unique autofluorescence intensity and fluorescence lifetime profiles. Additionally, qNSCs specifically display an enrichment of a specific autofluorescent signal localizing to lysosomes that is highly predictive of cell state. These signals can be used as a graded marker of NSC quiescence to predict cell behavior and track the dynamics of quiescence exit at single cell resolution in vitro and in vivo. Through coupling autofluorescence imaging with single-cell RNA sequencing in vitro and in vivo, we provide a high-resolution resource revealing transcriptional features linked to rapid NSC activation and deep quiescence. Taken together, we describe a single-cell resolution, non-destructive, live-cell, label-free strategy for measuring NSC activation state in vitro and in vivo and use this tool to expand our understanding of adult neurogenesis.

2024-02-09 | GSE223093 | GEO

Autofluorescence is a biomarker of neural stem cell activation state [Hippocampus]

2024-02-09 | GSE223092 | GEO

Epigenetic maintenance of neural stem cell quiescence in the adult mouse hippocampus via Setd1a [RNA-Seq]

Project description:Quiescence, a hallmark of adult neural stem cells (NSCs), is required for maintaining the NSC pool to support life-long continuous neurogenesis in the adult dentate gyrus (DG). Whether epigenetic mechanisms can maintain NSC quiescence over long term in the adult brain is not well-understood. Here we showed that adult mice with haploinsufficiency of Setd1a, a schizophrenia risk gene encoding a histone H3K4 methyltransferase, exhibited substantially enlarged DG with increased number of dentate granule cells. Deletion of Setd1a specifically in quiescent NSCs in the adult DG promoted their activation and neurogenesis, which was countered by inhibition of histone demethylase LSD1. Mechanistically, RNA sequencing and CUT & RUN analyses of cultured quiescent adult NSCs revealed Setd1a deletion-induced transcriptional changes and Setd1a targets, among which down-regulation of Bhlhe40 promoted quiescent NSC activation in the adult DG. Together, our study revealed a Setd1a-dependent epigenetic mechanism that sustains NSC quiescence in the adult DG.

2024-03-31 | GSE250276 | GEO

Epigenetic maintenance of neural stem cell quiescence in the adult mouse hippocampus via Setd1a [Cut & Run]

2024-03-31 | GSE250275 | GEO

A lysine demethylase-independent function of Phf2 regulates cohesin-mediated DNA replication for neural stem cell activation

Project description:The activation of quiescent neural stem cells (qNSCs) in the dentate gyrus is required for lifelong neurogenesis. However, the mechanisms that promote the exit of neural stem cells (NSCs) from quiescence remain elusive. We demonstrate that the expression of plant homeodomain finger protein 2 (Phf2) activates the exit of postnatal mouse NSC from shallow quiescence. Loss of Phf2 prevents NSC activation and neurogenesis in postnatal 30 (P30) mice but does not decrease the label-retaining NSC pool, indicating that Phf2 is not required for the exit of NSC from quiescence. NSC-specific deletion of Phf2 modestly compromises embryonic mouse NSC proliferation without increasing apoptosis, indicating that Phf2 is crucial for embryonic development. Moreover, human cortical organoids reveal that Phf2 promotes NPC proliferation via a lysine demethylase-independent manner. Mechanistically, Phf2 directly binds to the cohesion complex via Rad21 and regulates the DNA replication in mouse NSC by associating with the cohesion complex releasing protein Wapl activity. Our study identifies the Phf2-cohesin complex mediated DNA replication for neural stem cell activation in a lysine demethylase-independent manner.

2024-03-01 | PXD040515 | JPOST Repository

Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury

Project description:Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Single cell RNAseq of cells isolated from their in vivo niche in the subventricular zone, Striatum and Cortex during homeostasis as well as following ischemic injury. In total 272 single cells. (<WT>: homeostasis samples; <Ischemic_injured> and <Ischemic_injured_and_Interferon_gamma_knockout>: samples following ischemic injuried).

2015-07-31 | E-GEOD-67833 | biostudies-arrayexpress

Foxc1 reinforces quiescence in hair follicle stem cells

Project description:Quiescent stem cells are periodically activated to maintain tissue homeostasis or occasionally called into action upon injury. Molecular mechanisms that constitutively maintain stem cell identity or promote stem cell proliferation and differentiation upon activation have been extensively studied. However, it is unclear how quiescent stem cells maintain identity and reinforce quiescence when they transition from quiescence to activation. Here we show mouse hair follicle stem cell compartment induces a transcription factor, Foxc1, when activated. Importantly, deletion of Foxc1 in the activated but not quiescent stem cells compromises stem cell identity, fails to re-establish quiescence and subsequently drives premature stem cell activation.These findings uncover a dynamic, cell-intrinsic mechanism employed by hair follicle stem cells to reinforce stemness in response to activation. Poly(A)-enriched transcriptome RNA-seq on HFSCs isolated in WT and K14Cre cKO mice at anagen and early telogen stage of hair cycle.

2016-02-05 | E-GEOD-67404 | biostudies-arrayexpress

A screen for histone mutations that affect quiescence in S. cerevisiae.

Project description:Quiescence is a distinct cell cycle phase, termed G0, in which growth, transcription, translation, and replication are suppressed. Yeast cells enter G0 following glucose exhaustion but remain viable for an extended period and can re-enter the cell cycle when returned to glucose-rich medium. Quiescence is a feature of all organisms and is essential for the maintenance of stem cells and tissue renewal. Quiescence is also related to chronological lifespan (CLS) - or the capacity of post-mitotic quiescent cells to survive over time - and thus contributes to longevity. However, important questions remain to be answered regarding the mechanisms that control entry into quiescence, the maintenance of quiescence, and the re-entry of quiescent cells into the cell cycle. Histone acetylation is lost during the formation of quiescent yeast cells, and chromatin becomes highly condensed. This unique chromatin landscape plays a key role in supporting quiescence-specific transcriptional repression and has been linked to the formation and maintenance of quiescent cells. To ask if other chromatin features regulate quiescence, we conducted a comprehensive screen of histone H3 and H4 mutants. We identified several mutants that show altered quiescence entry and have characterized their chromatin phenotypes. None of these mutants retain histone acetylation, while several have altered chromatin condensation. Additionally, a screen for H3 and H4 mutants with altered chronological lifespan showed that CLS is highly correlated with quiescence entry.

2023-03-01 | GSE210305 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data