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Gene expression in adult neural precursor cells from the hippocampus or subventricular zone

ABSTRACT: Regulating the cell cycle entry of neural stem cells (NSCs) is critical for continued adult neurogenesis and is extensively shown to be subject to environmental modulation. Here we demonstrate that pro-proliferative stimulation by physical activity is achieved by activating quiescent hippocampal precursors. Using independent approaches, we show that differential enrichment of endogenous ROS distinguishes this pool of activatable, quiescent cells. Endogenous ROS content clusters Nestin (Nes)-GFP+ precursor cells into heterogeneous cell populations with unique transcriptional identities and significant changes in ROS content precede gene expression changes and neurogenic commitment. A sub-optimal physical activity triggers a ROS surge exclusively in cells with high intracellular ROS content underpinning their recruitment into active growth cycle. These ROS dynamics are independent of mitochondrial function and are driven by the activity of NADPH oxidising enzyme Nox2. While baseline neurogenesis is unaffected, ROS fluctuations and the pro-neurogenic response to physical activity was abolished in Nox2-deficient mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE123961 | GEO | 2020/09/25

REPOSITORIES: GEO

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Gene expression in classes of adult hippocampal precursor cells defined by ROS content

Project description:Regulating the cell cycle entry of neural stem cells (NSCs) is critical for continued adult neurogenesis and is extensively shown to be subject to environmental modulation. Here we demonstrate that pro-proliferative stimulation by physical activity is achieved by activating quiescent hippocampal precursors. Using independent approaches, we show that differential enrichment of endogenous ROS distinguishes this pool of activatable, quiescent cells. Endogenous ROS content clusters Nestin (Nes)-GFP+ precursor cells into heterogeneous cell populations with unique transcriptional identities and significant changes in ROS content precede gene expression changes and neurogenic commitment. A sub-optimal physical activity triggers a ROS surge exclusively in cells with high intracellular ROS content underpinning their recruitment into active growth cycle. These ROS dynamics are independent of mitochondrial function and are driven by the activity of NADPH oxidising enzyme Nox2. While baseline neurogenesis is unaffected, ROS fluctuations and the pro-neurogenic response to physical activity was abolished in Nox2-deficient mice.

2020-09-25 | GSE123960 | 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.

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Comprehensive proteome of the adult neural stem cell niche identifies key regulators of adult neurogenesis

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Female Mice Lacking p47phox Have Altered Adipose Tissue Gene Expression and are Protected against High Fat-Induced Obesity and Metabolic Syndrome

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Modulation of NOX2 causes Obesity- Mediated Atrial Fibrillation

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Female Mice Lacking p47phox Have Altered Adipose Tissue Gene Expression and are Protected against High Fat-Induced Obesity and Metabolic Syndrome

Project description:Oxidative stress in adipose tissue and liver has been linked to the development of obesity. NADPH oxidases (NOX) enzymes are a major source of reactive oxygen species (ROS). The current study was designed to determine if NOX2-generated ROS play a role in development of obesity and metabolic syndrome after high fat feeding. Wild type (WT) mice and mice lacking the cytosolic NOX2 activated protein p47phox (P47KO) were fed AIN-93G diets or high fat diets (HFD) containing 45% fat and 0.5% cholesterol for 13 weeks from weaning. Affymetrix array analysis revealed dramatically less expression of mRNA of genes linked to energy metabolism, adipocyte differentiation (PPARγ, Runx2) and fatty acid uptake (CD36, lipoprotein lipase) in fat pads from female HFD-P47KO mice compared to HFD-WT females. These data suggest that NOX2 is an important regulator of metabolic homeostasis and that NOX2-associated ROS plays an important role in development of diet-induced obesity particularly in the female

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2022-10-13 | PXD021376 | Pride

Transcription profiling of mouse functionally distinct radial glial subsets

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