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A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583518/ https://www.ncbi.nlm.nih.gov/pubmed/28854364 http://dx.doi.org/10.1016/j.celrep.2017.08.029 |
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author | Knobloch, Marlen Pilz, Gregor-Alexander Ghesquière, Bart Kovacs, Werner J. Wegleiter, Thomas Moore, Darcie L. Hruzova, Martina Zamboni, Nicola Carmeliet, Peter Jessberger, Sebastian |
author_facet | Knobloch, Marlen Pilz, Gregor-Alexander Ghesquière, Bart Kovacs, Werner J. Wegleiter, Thomas Moore, Darcie L. Hruzova, Martina Zamboni, Nicola Carmeliet, Peter Jessberger, Sebastian |
author_sort | Knobloch, Marlen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5583518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55835182017-09-14 A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity Knobloch, Marlen Pilz, Gregor-Alexander Ghesquière, Bart Kovacs, Werner J. Wegleiter, Thomas Moore, Darcie L. Hruzova, Martina Zamboni, Nicola Carmeliet, Peter Jessberger, Sebastian Cell Rep Article 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. Cell Press 2017-08-29 /pmc/articles/PMC5583518/ /pubmed/28854364 http://dx.doi.org/10.1016/j.celrep.2017.08.029 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Knobloch, Marlen Pilz, Gregor-Alexander Ghesquière, Bart Kovacs, Werner J. Wegleiter, Thomas Moore, Darcie L. Hruzova, Martina Zamboni, Nicola Carmeliet, Peter Jessberger, Sebastian A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity |
title | A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity |
title_full | A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity |
title_fullStr | A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity |
title_full_unstemmed | A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity |
title_short | A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity |
title_sort | fatty acid oxidation-dependent metabolic shift regulates adult neural stem cell activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583518/ https://www.ncbi.nlm.nih.gov/pubmed/28854364 http://dx.doi.org/10.1016/j.celrep.2017.08.029 |
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