MiR-153 overexpressing NSPCs derived from mouse ES cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jun Tsuyama
PROVIDER: E-GEOD-70129 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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.
2015-08-01 | GSE70129 | GEO
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: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 expression of the mciroRNA, miR-153 is significantly altered in neural stem cells (NSCs) following exposure to the teratogens, alcohol and nicotine (PMIDs:22458409, 17687032). To better understand how miR-153 may mediate teratogenesis, we first needed to identify miR153 targets in fetal NSCs. Gestational day 12.5 fetal mouse cortical neural epithelium was isolated and grown as neurospheres in defined medium for studies. We overexpressed miR-153 in fetal NSCs for 24 hours in a transient transfection assay, and profiled mRNA expression using a microarray platform (codelink array) to identify potential target genes. Over expression of pre-miR-153 resulted in a ~32-fold induction of miR-153 compared to the transfection control. Transcript profiles were assessed from RNA samples (6 independent replicates in each condition) hybridized to codelink microarrays according to manufacturer's protocols. Data analysis showed that miR-153 overexpression resulted in statistically significant down-regulation of 102 genes (at a false discovery rate α=0.1, of a total of 860 transcripts down-regulated by ≥1.3-fold). These data suggested the role of this miRNA in moderately controlling expression hundreds of gene transcripts. These regulated genes may be important in controlling neural stem cell differentiation and downstream signaling pathways.
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Project description:Since the NFI transcription factors have been shown to be key regulators of gliogenesis, we utilized this pathway to identify miRNAs involved in the regulation of the neurogenesis-to-gliogenesis switch by neural stem/progenitor cells (NSPCs). We focused on miRNAs with expression levels that were differentially regulated downstream of NFIA, and established a mouse embryonic stem cell (ESC) line that expresses NFIA in a doxycycline (Dox)-dependent manner. NFIA-overexpressing (OE) and control NSPCs (neurospheres) derived from ESCs were purified from their mixed cultures (primary neursphsres (PNs) or secondary neurospheres (SNs) ) by fluorescence activated cell sorting and subjected to miRNAarray analysis.
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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:Since the NFI transcription factors have been shown to be key regulators of gliogenesis, we utilized this pathway to identify miRNAs involved in the regulation of the neurogenesis-to-gliogenesis switch by neural stem/progenitor cells (NSPCs). We focused on miRNAs with expression levels that were differentially regulated downstream of NFIA, and established a mouse embryonic stem cell (ESC) line that expresses NFIA in a doxycycline (Dox)-dependent manner. NFIA-overexpressing (OE) and control NSPCs (neurospheres) derived from ESCs were purified from their mixed cultures (primary neursphsres (PNs) or secondary neurospheres (SNs) ) by fluorescence activated cell sorting and subjected to the gene expression microrray analysis.
2015-08-01 | E-GEOD-70130 | biostudies-arrayexpress
Project description:The expression of the mciroRNA, miR-153 is significantly altered in neural stem cells (NSCs) following exposure to the teratogens, alcohol and nicotine (PMIDs:22458409, 17687032). To better understand how miR-153 may mediate teratogenesis, we first needed to identify miR153 targets in fetal NSCs. Gestational day 12.5 fetal mouse cortical neural epithelium was isolated and grown as neurospheres in defined medium for studies. We overexpressed miR-153 in fetal NSCs for 24 hours in a transient transfection assay, and profiled mRNA expression using a microarray platform (codelink array) to identify potential target genes. Over expression of pre-miR-153 resulted in a ~32-fold induction of miR-153 compared to the transfection control. Transcript profiles were assessed from RNA samples (6 independent replicates in each condition) hybridized to codelink microarrays according to manufacturer's protocols. Data analysis showed that miR-153 overexpression resulted in statistically significant down-regulation of 102 genes (at a false discovery rate α=0.1, of a total of 860 transcripts down-regulated by ≥1.3-fold). These data suggested the role of this miRNA in moderately controlling expression hundreds of gene transcripts. These regulated genes may be important in controlling neural stem cell differentiation and downstream signaling pathways. Six independent replicates were performed for control and treatment groups, and twelve independent single channel intensity values were uploaded after normalization for analysis independent single channel intensity values were uploaded after normalization
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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: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.
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