Ontology highlight
ABSTRACT:
PROVIDER: PRJEB27614 | ENA |
REPOSITORIES: ENA
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Project description:Id4 maintains quiescence of adult hippocampal stem cells
| PRJNA480836 | ENA
Project description:Neural stem cells (NSCs) are multipotent cells in the central nervous system which can self-renew, differentiate or reversibly exit the cell cycle to enter a dormat state known as quiescence. To study the molecular mechanisms underpinning this state we use an in vitro model of NSC quiescence, which uses adult hippocampal NSCs harvested from mice. In this cell culture system, we are able to reversibly induce quiescence by supplementing the media with BMP4. In this study we examine how the proteome changes as NSCs transition from an active state (proliferating, 0d BMP4) into quiescence (up to 21 days in BMP4).
2026-03-09 | PXD037487 | Pride
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
Project description:Chronic stress inhibits neurogenesis, yet its impact on neural stem cells (NSCs) remains poorly understood. Here, using the 5-bromo-2′-deoxyuridine (BrdU) label-retaining assay, we found that chronic restraint stress (CRS) in adult mice promoted quiescence in hippocampal NSCs (i.e. radial-glial-like cells, RGLs). Long-term administration of the synthetic stress hormone agonist dexamethasone (Dex) to adult mice recapitulated the phenotype. Moreover, pre-administration of the antagonist mifepristone (RU486) prevented RGLs from quiescence. At the cellular level, Dex induced reversible quiescence in hippocampal NSCs (HpNSCs) in a manner similar to the quiescence-promoting signal BMP4 in vitro. However, Dex and BMP4 regulated overlapping yet distinct NSC quiescence programs, with their co-regulation primarily being synergistic. Mechanistically, Dex downregulated the expression of achaete-scute homolog 1 (Ascl1) by repressing a distal enhancer. These data suggest that chronic stress induces quiescence in RGLs by repressing the transcription of the quiescence regulator gene Ascl1, and that synthetic glucocorticoid antagonists may have therapeutic value in correcting abnormalities of NSC activity in conditions associated with elevated cortisol levels, including psychological and mental health conditions.
2026-03-20 | GSE262991 | GEO
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
Project description:Chronic stress inhibits neurogenesis, yet its impact on neural stem cells (NSCs) remains poorly understood. Here, using the 5-bromo-2′-deoxyuridine (BrdU) label-retaining assay, we found that chronic restraint stress (CRS) in adult mice promoted quiescence in hippocampal NSCs (i.e. radial-glial-like cells, RGLs). Long-term administration of the synthetic stress hormone agonist dexamethasone (Dex) to adult mice recapitulated the phenotype. Moreover, pre-administration of the antagonist mifepristone (RU486) prevented RGLs from quiescence. At the cellular level, Dex induced reversible quiescence in hippocampal NSCs (HpNSCs) in a manner similar to the quiescence-promoting signal BMP4 in vitro. However, Dex and BMP4 regulated overlapping yet distinct NSC quiescence programs, with their co-regulation primarily being synergistic. Mechanistically, Dex downregulated the expression of achaete-scute homolog 1 (Ascl1) by repressing a distal enhancer. These data suggest that chronic stress induces quiescence in RGLs by repressing the transcription of the quiescence regulator gene Ascl1, and that synthetic glucocorticoid antagonists may have therapeutic value in correcting abnormalities of NSC activity in conditions associated with elevated cortisol levels, including psychological and mental health conditions.
2026-03-20 | GSE262992 | GEO
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
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
Project description:<p>Anxiety is an aggravating comorbidity of many psychiatric disorders that is often underdiagnosed and undertreated, and little is known on the mechanisms underlying its regulation. Here, we find that serum LPA16:0 abundance increases with trait anxiety in both humans and mice; while high LPA16:0 levels are sufficient to reduce the in vitro proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor LPA1, bears single nucleotide polymorphism variants associated with anxiety. In mice, LPA16:0 decreases hippocampal neurogenesis and stress resilience, whereas LPA1 antagonism or the reduction of platelets, the main source of circulating LPA16:0, increases adult neurogenesis and resilience to acute stress. Conditional knockdown of LPA1 receptor in neural stem cells is sufficient to enhance cell proliferation in the dentate gyrus. Finally, the inhibition of adult neurogenesis abolishes the beneficial effect of LPA1 antagonism on resilience against both acute and chronic stress. Together, these findings identify circulating LPA16:0 as a biomarker of trait anxiety and LPA16:0-LPA1 signaling as a regulation mechanism of mood-related behavior through the decrease of adult neurogenesis.</p>
2026-02-05 | MTBLS13589 | MetaboLights
Project description:Postnatal neural stem cells are primarily quiescent, which is a cellular state that exists as a continuum from deep to shallow quiescence. The molecular changes that occur along this continuum are beginning to be understood but the transcription factor network governing these changes has not been defined. We show that these transitions are regulated by sequential transcription factor programs. Single-cell transcriptomic analyses of mice with loss- or gain-of-function of the essential activation factor Ascl1, reveal that Ascl1 promotes the activation of hippocampal neural stem cells by driving these cells out of deep quiescence, despite its low protein expression. Subsequently, during the transition from deep to shallow quiescence, Ascl1 induces the expression of Mycn, which drives progression through shallow states of quiescence towards an active state. Together, these results define the required sequence of transcription factors during hippocampal neural stem cell activation.
2025-03-16 | GSE280296 | GEO