A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity.

Détails

Ressource 1Télécharger: Cell Reports 2017 Knobloch.pdf (16966.44 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_09A7951D55FF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity.
Périodique
Cell Reports
Auteur(s)
Knobloch M., Pilz G.A., Ghesquière B., Kovacs W.J., Wegleiter T., Moore D.L., Hruzova M., Zamboni N., Carmeliet P., Jessberger S.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
20
Numéro
9
Pages
2144-2155
Langue
anglais
Résumé
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.

Mots-clé
beta-oxidation, hippocampus, metabolism, neural stem cell, neurogenesis, proliferation, quiescence
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/12/2017 15:38
Dernière modification de la notice
20/08/2019 13:31
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