Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE168189 | GEO | 2021/03/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

LRIG1 controls proliferation of adult neural stem cells by facilitating Tgfß and BMP signalling pathways

Project description:Adult Neural Stem Cells (aNSCs) in the ventricular-subventricular zone (V-SVZ) are largely quiescent. Here, we characterize the mechanism underlying the functional role of a cell-signalling inhibitory protein, LRIG1, in the control of aNSCs proliferation. Using constitutive Lrig1 knockout models, we show that Lrig1 ablation results in increased aNSCs proliferation with no change in neuronal progeny and that this hyperproliferation likely does not result from activation of the epidermal growth factor receptor (EGFR). Loss of LRIG1, however, does lead to impaired activation of canonical transforming growth factor beta (TGFβ) and bone morphogenic protein (BMP) signalling pathways. Biochemically, we show in vitro that LRIG1 is able to bind TGFβ/BMP receptors and the TGFβ1 ligand. Finally, we show that the consequences of these interactions are to facilitate SMAD phosphorylation and pathway activation. Collectively, these data suggest that, unlike in embryonic neural stem cells where EGFR is the primary mechanism of action, LRIG1 and TGFβ pathways positively work together to fulfill their inhibitory roles in aNSCs.

2024-07-08 | GSE263575 | GEO

RNA-sequencing gene expression data from FACS-purified Ventricular-Subventricular Zone (V-SVZ) and cortical cells from hGFAP::GFP mice.

Project description:Quiescent neural stem cells (NSCs) in the adult ventricular-subventricular zone (V-SVZ) undergo activation and divide to generate neurons and glia. Here we show that Platelet-derived Growth Factor Receptor beta (PDGFRβ) is expressed by quiescent and early activated adult V-SVZ NSCs, and maintains their quiescence. We further showed that selective deletion of PDGFRβ in adult V-SVZ NSCs leads to activation of quiescent NSCs. We performed RNA-seq on FACS-sorted V-SVZ quiescent, early activated and late activated NSCs, as well as cortical cells from adult 2-4 month old mice.

2021-05-01 | GSE118009 | GEO

Single cell analysis of the postnatal dorsal V-SVZ reveals a role for Bmpr1a-signaling in silencing pallial germinal activity

Project description:The ventricular-subventricular zone (V-SVZ) is the largest neurogenic region of the postnatal forebrain, containing neural stem cells (NSCs) that emerge from both the embryonic pallium and subpallium. Despite of this dual origin, glutamatergic neurogenesis declines rapidly after birth, while gabaergic neurogenesis persists throughout life. We performed single-cell RNA-sequencing (scRNA-Seq) of the postnatal dorsal V-SVZ for unravelling the mechanisms leading to pallial lineage germinal activity silencing. We show that pallial NSCs enter a state of deep quiescence, characterized by high BMP-signaling, reduced transcriptional activity and Hopx expression, whilst in contrast, subpallial NSCs remain primed for activation. Induction of deep quiescence is paralleled by a rapid blockade of glutamatergic neurons production and differentiation. Finally, manipulation of Bmpr1a demonstrates its key role in mediating these effects. Together, our results highlight a central role of BMP-signaling in synchronizing quiescence induction and blockade of neuronal differentiation to rapidly silence pallial germinal activity after birth.

2023-05-02 | GSE186003 | GEO

Real-time quantitative PCR analysis of microRNAs expressed in adult mouse ventricular-subventricular zone cell populations

Project description:Total RNA was isolated from GFAP::GFP+CD133+EGFR-CD24- (quiescent neural stem cells, qNSCs), GFAP::GFP+CD133+EGFR+CD24- (activated neural stem cells, aNSCs) and GFAP::GFP+CD133- EGFR+CD24- (transit amplifying cells, TACs) cells from the adult mouse ventricular-subventricular zone (V-SVZ) (GFAP::GFP mice, Jackson Mice Stock number 003257).

2022-12-05 | GSE217425 | 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

Single-cell RNA-sequencing of adult neural stem cells reveals novel molecular principles of stem cell activation and heterogeneity

Project description:Neural stem cells (NSCs) in the subventricular zone (SVZ) and the subgranular zone of the hippocampus continuously give rise to glial cells and neurons and are the most important source for new neurons in the adult mammalian brain1-4. It has been suggested that the NSCs in the adult brain form a heterogeneous population5,7, akin to other tissue-specific adult stem cells6. However, a molecular basis of the presumed NSC heterogeneity has been lacking. Here, we sequenced the transcriptomes of 131 individual adult NSCs from the mouse SVZ. After filtering, 117 cells were used for further analysis. We found that they consist of two distinct subgroups of about equal size, independent of the mouse’s age. These subgroups were separated by molecular markers of quiescence (quiescent NSCs, qNSCs) and cell-cycle progression (active NSCs, aNSCs). We identified novel cell surface markers belonging to the tetraspanin family of transmembrane proteins for the prospective purification of qNSCs and aNSCs. The individual NSC transcriptomes were ordered along a continuous progression from qNSCs to aNSCs, with the expression of molecular pathways decreasing (G-protein-coupled receptor signaling) or increasing (MAP kinase, PI3 kinase-mTOR, Hippo, and p53 pathways) in a coordinated manner. Within the aNSCs, transcription factors for neural cell lineage specification were expressed in patterns that indicate specific lineage commitment of individual aNSC. Together, these findings imply that the switch from qNSC to aNSC is irreversible in vivo, at least in a large fraction of cells, and is accompanied by lineage commitment already at the stem-cell stage. Thus our work reveals coherent patterns of molecular heterogeneity within adult NSCs that arise from the regulation of cell-cycle activity and differentiation pathways. We also sequenced 13 bulk populations.

2021-12-31 | GSE66460 | GEO

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

Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone in vitro

Project description:Bone morphogenetic protein-4 (BMP4) is involved in regulation of neural stem cells (NSCs) proliferation, differentiation, migration and survival. It was previously thought that the treatment of NSCs with BMP4 alone induces astrocytes, whereas the treatment of NSCs with the bFGF/BMP4 combination induces quiescent neural stem cells (qNSCs). In this study, we performed RNA sequencing (RNA-Seq) to compare the transcriptome profiles of BMP4-treated NSCs and bFGF/BMP4-treated NSCs, and found that both NSCs treated by these two methods were Sox2 positive qNSCs which were able to generate neurospheres. However, NSCs treated by those two methods exhibited different characteristics in state and the potential for neuronal differentiation based on transcriptome analysis and experimental results. We found that BMP4-treated NSCs tended to be in a deeper quiescent state than bFGF/BMP4-treated NSCs as the percentage of ki67-positive cells were lower in BMP4-treated NSCs. And after exposure to differentiated environment, bFGF/BMP4-treated NSCs generated more DCX-positive immature neurons and MAP2-positive neurons than BMP4-treated NSCs. Our study characterized qNSCs treated with BMP4 alone and bFGF/BMP4 combination, which laid a foundation for studying the activation mechanism of qNSCs.

2024-06-26 | GSE267115 | GEO

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

2015-07-31 | GSE67833 | GEO