Genomic Glucocorticoid Action in Embryonic Mouse Neural Stem Cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE222392 | GEO | 2023/01/11
REPOSITORIES: GEO
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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:The transition between quiescence and activation in neural stem and progenitor cells (NSPCs) is coupled to reversible changes in energy metabolism with key implications for life-long NSPC self-renewal and neurogenesis. How this metabolic plasticity is ensured between NSPC activity states is unclear. We find that a state-specific rewiring of the mitochondrial proteome by the i-AAA peptidase YME1L is required to preserve NSPC self-renewal. YME1L controls the abundance of numerous mitochondrial substrates in quiescent NSPCs, and its deletion activates a differentiation program characterized by broad metabolic changes causing the irreversible shift away from a fatty acid oxidation-dependent state. Conditional Yme1l deletion in adult NSPCs in vivo results in defective self-renewal and premature differentiation, ultimately leading to NSPC pool depletion. Our results disclose an important role for YME1L in coordinating the switch between metabolic states of NSPCs and suggest that NSPC fate is regulated by compartmentalized changes in protein network dynamics.
2022-02-10 | PXD030995 | Pride
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:Mammalian neural stem/progenitor cells (NSPCs) sequentially generate neurons and glia during central nervous system (CNS) development. Several transcription factors and microRNAs (miRNAs) are involved in the temporal regulation of NSPC differentiation. miRNA-153 (miR-153) as a modulator of NSPC specification. Overexpression (OE) of miR-153 delayed the onset of astrogliogenesis and maintained NSPCs in an undifferentiated state in vitro. miR-153-OE and control NSPCs (tertiary neurospheres (TNs) derived from mouse ES Cells via embryoid body formation) subjected to the gene expression microarray analysis.
2015-08-01 | E-GEOD-70129 | biostudies-arrayexpress
Project description:Histone deacetylase 3 (HDAC3) is a unique epigenetic regulator forming stoichiometric complexes with several other proteins. Patients with mutations in genes encoding these proteins display intellectual disability, implying an important role of HDAC3 in this prevalent disease. Here we report that cerebrum-specific inactivation of the mouse gene causes striking developmental defects in the neocortex, hippocampus and corpus callosum; post-weaning lethality; and abnormal behaviors, including hyperactivity and anxiety. The developmental defects are due to rapid loss of neural stem and progenitor cells (NSPCs), starting at E14.5. Premature neurogenesis and abnormal neuronal migration in the mutant brain alter NSPC homeostasis. Mutant cerebral cortices display augmented DNA damage, apoptosis, and histone hyperacetylation. In agreement with these results, mutant NSPCs are impaired in forming neurospheres in vitro, and treatment of wild-type NSPCs with the HDAC3-specific inhibitor RGFP966 abolishes neurosphere formation. Transcriptomic analyses of neonatal cerebral cortices and cultured neurospheres support that HDAC3 regulates various transcriptional programs through interaction with multiple transcription factors, including NFIB. These findings establish HDAC3 as a major deacetylase critical for perinatal development of the mouse cerebrum and NSPCs, thereby suggesting a direct link of this enzymatic epigenetic regulator to human cerebral and intellectual development. To study the impact of cerebrum specific (Emx1-Cre) deletion of Hdac3 on embryonic neurospheres (cultured in vitro from E16.5 cerebrum) and neocortex from newborn pups (P0).
2019-06-25 | GSE133195 | GEO
Project description:We checked whether the inhibition of the FGF, VEGF, and TGF signaling pathways would influence the miRNA profile in ECs, co-cultured with NSPCs. EC/NSPC co-cultures were incubated with FGF/VEGF receptor inhibitor PD 173074 (1μM in DMSO), and the TGF-β receptor inhibitor SB431542 (10μM in DMSO, Millipore)
2012-01-01 | E-GEOD-32352 | biostudies-arrayexpress
Project description:Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age, but the molecular mechanisms responsible for these declines remain unclear. Here we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical for oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon injury. These phenotypes recapitulate defects in NSPCs during aging, implicating Nampt-mediated NAD+ biosynthesis as a mediator of these age-associated functional declines. Total RNA obtained from neurospheres derived from postnatal hippocampi subjected to 48 hours in vitro of incubation with Nampt-specific inhibitor FK866 (10 nM, 4 samples) or vehicle (DMSO, 1:1000, 4 samples).
2014-05-08 | E-GEOD-49784 | biostudies-arrayexpress
Project description:Neural stem/progenitor cells (NSPCs) generate new neurons throughout adulthood. However, the underlying regulatory processes are still not fully understood. Lipid metabolism plays an important role in regulating NSPC activity: build-up of lipids is crucial for NSPC proliferation, whereas break-down of lipids has been shown to regulate NSPC quiescence. Despite their central role for cellular lipid metabolism, the role of lipid droplets (LDs), the lipid storing organelles, in NSPCs remains underexplored. Here we show that LDs are highly abundant in adult mouse NSPCs, and that LD accumulation is significantly altered upon fate changes such as quiescence and differentiation. NSPC proliferation is influenced by the number of LDs, inhibition of LD build-up, breakdown or usage, and the asymmetric inheritance of LDs during mitosis. Furthermore, high LD-containing NSPCs have increased metabolic activity and capacity, but do not suffer from increased oxidative damage. Together, these data indicate an instructive role for LDs in driving NSPC behaviour.
2021-11-10 | GSE187470 | GEO
Project description:The transition between quiescence and activation in neural stem and progenitor cells (NSPCs) is coupled to reversible changes in energy metabolism with key implications for life-long NSPC self-renewal and neurogenesis. How this metabolic plasticity is ensured between NSPC activity states is unclear. We find that a state-specific rewiring of the mitochondrial proteome by the i-AAA peptidase YME1L is required to preserve NSPC self-renewal. YME1L controls the abundance of numerous mitochondrial substrates in quiescent NSPCs, and its deletion activates a differentiation program characterized by broad metabolic changes causing the irreversible shift away from a fatty acid oxidation-dependent state. Conditional Yme1l deletion in adult NSPCs in vivo results in defective self-renewal and premature differentiation, ultimately leading to NSPC pool depletion. Our results disclose an important role for YME1L in coordinating the switch between metabolic states of NSPCs and suggest that NSPC fate is regulated by compartmentalized changes in protein network dynamics.
2022-01-19 | GSE193551 | GEO
Project description:Mechanisms controlling the proliferative activity of neural stem/progenitor cells (NSPCs) play a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of FASN in NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for FASN to fuel lipogenesis. Thus, we here identified a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation. 6 samples were analyzed. Spot14+: Spot14 GFP positive mouse neural stem cell, 3 biological rep Spot14-: Spot14 GFP negative mouse neural stem cell, 3 biological rep
2012-11-02 | E-GEOD-27391 | biostudies-arrayexpress