Publikationsdatum:
2012-12-04
Beschreibung:
Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587167/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587167/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knobloch, Marlen -- Braun, Simon M G -- Zurkirchen, Luis -- von Schoultz, Carolin -- Zamboni, Nicola -- Arauzo-Bravo, Marcos J -- Kovacs, Werner J -- Karalay, Ozlem -- Suter, Ueli -- Machado, Raquel A C -- Roccio, Marta -- Lutolf, Matthias P -- Semenkovich, Clay F -- Jessberger, Sebastian -- P30 DK020579/DK/NIDDK NIH HHS/ -- R01 DK076729/DK/NIDDK NIH HHS/ -- R01 DK088083/DK/NIDDK NIH HHS/ -- England -- Nature. 2013 Jan 10;493(7431):226-30. doi: 10.1038/nature11689. Epub 2012 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain Research Institute, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23201681" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Adult Stem Cells/cytology/*metabolism
;
Animals
;
Cell Proliferation
;
Dentate Gyrus/metabolism
;
Fatty Acid Synthases/deficiency/genetics/*metabolism
;
Gene Expression Profiling
;
Hippocampus/cytology/metabolism
;
*Lipogenesis
;
Malonyl Coenzyme A/metabolism
;
Mice
;
Mice, Transgenic
;
Neural Stem Cells/cytology/*metabolism
;
Neurogenesis
;
Nuclear Proteins/genetics/metabolism
;
Transcription Factors/genetics/metabolism
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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