A fatty acid oxidation-dependent metabolic shift regulates adultneural stem cell activity

Open access
Date
2017-08Type
- Journal Article
Citations
Cited 156 times in
Web of Science
Cited 154 times in
Scopus
ETH Bibliography
yes
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Abstract
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. Here, we show that the rate of fatty acid oxidation (FAO) regulates the activity of 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, 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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000191620Publication status
publishedExternal links
Journal / series
Cell ReportsVolume
Pages / Article No.
Publisher
Cell PressSubject
Neurogenesis; Neural stem cell; Hippocampus; Beta-oxidation; Metabolism; Proliferation; QuiescenceOrganisational unit
08839 - Zamboni, Nicola (Tit.-Prof.)
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
03713 - Sauer, Uwe / Sauer, Uwe
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Show all metadata
Citations
Cited 156 times in
Web of Science
Cited 154 times in
Scopus
ETH Bibliography
yes
Altmetrics