Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE67833 | GEO | 2015/07/31

SECONDARY ACCESSION(S): PRJNA281015

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

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

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

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

SETD4 Cells Contribute to Brain Development and Maintain Adult Stem Cell Reservoir for Neurogenesis

Project description:Cellular quiescence facilitates maintenance of neural stem cells (NSCs) and their subsequent regenerative functions in response to brain injury and aging. However, the specification and maintenance of NSCs in quiescence from embryo to adulthood remains largely unclear. Here, using Set domain-containing protein 4 (SETD4), an epigenetic determinant of cellular quiescence, we mark a small but long-lived NSC population in deep quiescence in the subventricular zone of adult murine brain. Genetic lineage tracing shows that SETD4+ cells appear before neuroectoderm formation and contribute to brain development. In the adult, conditional knock-out of SETD4 resulted in quiescence exit of NSCs, generating newborn neurons in the olfactory bulb and contributing to damage repair. However, long period deletion of SETD4 lead to exhaustion of NSC reservoir or SETD4 overexpression caused quiescence entry of NSCs, leading to suppressed neurogenesis. This study reveals the existence of long-lived deep quiescent NSCs and their neurogenetic capacities beyond activation.

2022-08-25 | GSE200159 | GEO

Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) controls hippocampal neural stem cell conversion into progenitor cells

Project description:Neural stem cells (NSCs) continuously produce new neurons within the adult mammalian hippocampus. However, this process declines with age and this decline correlates with defects in cognitive function and mood. Molecular mechanisms that activate quiescent NSCs to generate progenitor cells in vivo remain poorly understood. Here we show that adult hippocampal NSCs express VEGFR3, a key regulator of vascular and neural development, and are activated by the VEGFR3 ligand VEGF-C to enter the cell cycle and convert into progenitor cells. Conditional deletion of Vegfr3 in NSCs leads to a decline in hippocampal neurogenesis. Functionally, this is associated with increased anxiety behavior and compromised NSC activation in response to VEGF-C and physical activity. These findings establish VEGFR3 expression as a hallmark of adult mouse NSCs and demonstrate a specific requirement for VEGF-C/VEGFR signaling in NSC activation. Enhancing VEGFR3 signaling by VEGF-C may improve neurogenesis and mood during aging.

2014-03-06 | GSE55621 | GEO

Molecular Cascade Reveals Sequential Milestones Underlying Hippocampal Neural Stem Cell Development into an Adult State

Project description:Quiescent adult neural stem cells (NSCs) in the mammalian brain arise from proliferating NSCs during development. Beyond acquisition of quiescence, an adult NSC hallmark, little is known about the process, milestones and mechanisms underlying the transition of developmental NSCs to an adult NSC state. Here we performed targeted single-cell RNA-seq analysis to reveal the molecular cascade underlying NSC development in the early postnatal mouse dentate gyrus. We identified two sequential steps, first a transition to quiescence followed by further maturation, each of which involved distinct changes in metabolic gene expression. Direct metabolic analysis uncovered distinct milestones, including an autophagy burst before NSC quiescence acquisition and cellular ROS level elevation along NSC maturation. Functionally, autophagy is important for the NSC transition to quiescence during early postnatal development. Together, our study reveals a multi-step process with defined milestones underlying establishment of the adult NSC pool in the mammalian brain.

2024-06-05 | GSE232833 | GEO

Lipidomic profiling reveals age-dependent changes in complex plasma membrane lipids that regulate neural stem cell aging (Part 1)

Project description:The aging brain exhibits a decline in the regenerative populations of neural stem cells (NSCs), which may underlie age-associated defects in sensory and cognitive functions1-4 . While mechanisms that restore old NSC function have started to be identified5-9 , the role of lipids – especially complex lipids – in NSC aging remains largely unclear. Using lipidomic profiling by mass spectrometry, we identify age-related lipidomic signatures in young and old quiescent NSCs in vitro and in vivo. These analyses reveal drastic changes in several complex membrane lipid classes, including phospholipids and sphingolipids in old NSCs. Moreover, polyunsaturated fatty acids (PUFAs) strikingly increase across complex lipid classes in quiescent NSCs during aging. Lipidomic profiling of isolated plasma membrane vesicles shows that agerelated differences in complex lipid levels and side chain composition are largely occurring in plasma membrane lipids. Experimentally, we find that aging is accompanied by modifications in membrane biophysical properties, with a decrease in plasma membrane order in old quiescent NSCs in vitro and in vivo. To determine the functional role of plasma membrane lipids in aging NSCs, we perform genetic and supplementations studies. Knockout of Mboat2, which encodes a phospholipid acyltransferase, exacerbates age-related lipidomic changes in old quiescent NSCs and impedes their ability to activate. As Mboat2 expression declines with age, Mboat2 deficiency may drive NSC decline during aging. Interestingly, supplementation of plasma membrane lipids derived from young NSCs boosts the ability of old quiescent NSCs to activate. Our work could lead to lipid-based strategies for restoring the regenerative potential of NSCs in old individuals, which has important implications to counter brain decline during aging.

2022-08-12 | ST002257 | MetabolomicsWorkbench

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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