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Id4 maintains quiescence of adult hippocampal stem cells

ABSTRACT: Id4 maintains quiescence of adult hippocampal stem cells

PROVIDER: PRJNA480836 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7514760.fastq.gz	Fastqsanger.gz
	SRR7514761.fastq.gz	Fastqsanger.gz
	SRR7514752.fastq.gz	Fastqsanger.gz
	SRR7514762.fastq.gz	Fastqsanger.gz
	SRR7514753.fastq.gz	Fastqsanger.gz

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Id4 maintains quiescence of adult hippocampal stem cells

Project description:Quiescence is essential for the long term maintenance of adult stem cells and tissue homeostasis. However, how stem cells maintain quiescence is still poorly understood. Here we show that stem cells in the dentate gyrus of the adult hippocampus actively transcribe the proactivation factor Ascl1 regardless of their activation state. We found that the inhibitor of DNA binding protein Id4 suppresses Ascl1 activity in neural stem cell cultures. Id4 sequesters Ascl1 heterodimerisation partner, promoting the degradation of Ascl1 protein and neural stem cell quiescence. Accordingly, elimination of Id4 from stem cells in the adult hippocampus results in abnormal accumulation of Ascl1 protein and premature stem cell activation. We also found that multiple signalling pathways converge on the regulation of Id4 to control the activity of hippocampal stem cells. Id4 therefore maintains quiescence of adult neural stem cells, in sharp contrast with its role of promoting the proliferation of embryonic neural progenitors.

2019-10-18 | GSE116997 | GEO

Intracrine Vascular Endothelial Growth Factor Maintains Hippocampal Neural Stem Cell Quiescence

Project description:Intracrine Vascular Endothelial Growth Factor Maintains Hippocampal Neural Stem Cell Quiescence

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Intracrine Vascular Endothelial Growth Factor Maintains Hippocampal Neural Stem Cell Quiescence

Project description:In the dentate gyrus (DG) of the adult mouse hippocampus, neural stem cells (NSCs) balance self-renewal and differentiation to produce neurons that support hippocampal function. Vascular endothelial growth factor (VEGF) is a well-known supporting factor for adult neurogenesis, but conflicting studies have left it uncertain how VEGF signals to NSCs. Here, we identified a VEGF-VEGFR2 intracrine signaling mechanism within adult DG NSCs that prevents their exhaustion. We show both in vitro and in vivo that NSC-VEGF loss caused cell-autonomous exhaustion of adult DG NSCs. In contrast, extracellular VEGF was neither necessary nor sufficient to maintain NSC quiescence or to stimulate VEGFR2 signaling, most likely due to sheddase-mediated cleavage of extracellular VEGFR2 ligand binding domains. Our findings support an exclusively intracellular mechanism for VEGF signaling in adult DG NSCs, thereby providing resolution to previously conflicting studies and suggesting cellular source can dictate the functional impact of soluble ligands in DG NSCs.

2024-04-16 | GSE220871 | GEO

C1 single-cell RNA-seq of Adult ID4-EGFP mouse spermatoognia

Project description:To reveal distinct transcriptomes associated with spermatogonial stem cell renewal vs. initiation of differentiation, single-cell transcriptomes from Adult ID4-EGFP+ spermatogonia were subdivided into subpopulations that displayed distinct fates when assayed by transplantation, with ID4-EGFPbright cells highly enriched for SSCs, and ID4-EGFPdim cells enriched for progenitors. We used the Fluidigm C1 instrument to capture individual spermatogonia for SMART-Seq2 single-cell RNA-seq.

2018-11-06 | GSE108974 | GEO

A fatty acid oxidation-dependent metabolic shift regulates adult neural stem cell quiescence

Project description:Adult hippocampal neurogenesis is important for certain forms of cognition and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. However, how this balance is regulated remains poorly understood. Here we show that the rate of fatty acid oxidation (FAO) defines quiescence vs. proliferation in NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs. Pharmacological inhibition and conditional deletion of Cpt1a in vitro and in vivo leads to altered NSPC behavior, showing that Cpt1a-dependent FAO is required for stem cell maintenance and proper neurogenesis. Strikingly, experimental manipulation of malonyl-CoA, the metabolite that regulates levels of FAO, is sufficient to induce exit from quiescence and to enhance NSPC proliferation. Thus, the data presented here identify a shift in FAO metabolism that governs NSPC behavior and suggest an instructive role for fatty acid metabolism in regulating NSPC activity.

2019-11-15 | PXD005598 | Pride

Converged Epitranscriptomic Co-regulation of TGFβ Signaling Components Suppresses the Quiescence Transition of Early Postnatal Hippocampal Neural Stem Cells

Project description:Quiescence acquisition of proliferating neural stem cells (NSCs) is required to establish the adult NSC pool yet the underlying molecular mechanisms are not well-understood. Here we showed that conditional deletion of the m6A reader Ythdf2, which promotes mRNA decay, in proliferating NSCs in the early postnatal mouse hippocampus led to elevated quiescence acquisition with decreased neurogenesis. Multimodal profiling of m6A modification, YTHDF2 binding, and mRNA decay in hippocampal NSCs identified shared targets in multiple TGFβ signaling pathway components, including TGFβ ligands, maturation factors, receptors, transcription regulators, and signaling regulators. Functionally, Ythdf2 deletion led to TGFβ signaling activation in NSCs, suppression of which rescued elevated quiescence acquisition of proliferating hippocampal NSCs. Our study reveals the dynamic nature and critical roles of mRNA decay in establishing the quiescent adult hippocampal NSC pool and uncovers a novel mode of epitranscriptomic control via co-regulation of multiple components of the same signaling pathway.

2024-08-26 | GSE266096 | GEO

RACK1 maintains mouse hematopoietic stem cell quiescence

Project description:RACK1 maintains mouse hematopoietic stem cell quiescence

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10x Genomics single-cell RNA-seq of isolated Adult ID4-EGFP-bright mouse spermatogonia treated with Rapamycin

Project description:To reveal distinct transcriptome changes among ID4-EGFP-bright adult mouse spermatogonia associated with mTORC1 activity, single-cell transcriptomes were generated from GFP-bright/CD9-bright spermatogonia from adult mice in three groups: control (untreated), 2 days of Rapamycin treatment (Rapamycin) and 2 days Rapamycin plus 1 day washout (Rapamycin_Release). Based on transplantation studies performed previously, ID4-EGFPbright cells are highly enriched for SSCs. We used the 10x Genomics Chromium to perform single-cell RNA-seq.

2021-02-18 | GSE152930 | GEO

Expression data from proliferating and quiescent adult hippocampal neural stem and progenitor cells

Project description:We have characterized the transcriptome of adult rat hippocampal neural stem and progenitor cell (NSPC) cultures. The NSPCs cultures can be reversibly arrested by the quiescence-promoting signal BMP4. We provide expression data from NSPCs grown as neurospheres for 4 days in vitro in the presence of FGF2 (proliferating NSPCs) or FGF2+BMP4 (quiescent NSPCs) showing that entry into quiescence involves major changes in the transcriptional profile of the cells.

2020-09-29 | GSE158658 | GEO

RNA sequencing of ID4-GFP Bright and ID4-GFP Dim spermatogonia from postnatal day 8 transgenic Id4-Gfp (LT11) mouse pups and ID4-GFP+ spermatogonia from ID4 overexpression mouse model and control

Project description:Mice that constitutively overexpress ID4 in germ cells have impaired spermatogenic lineage development. The transcriptome of ID4-GFP+ spermatogonia from testes of ID4 overexpression animals was compared to the ID4-GFP+ population from controls

2017-01-20 | GSE93866 | GEO

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