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Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis
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Journal Article
Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis
2013
Overview
Adult neural stem and progenitor cells (NSPCs) show high levels of fatty acid synthase (Fasn)-dependent
de novo
lipogenesis, a process that is controlled by Spot14 to regulate the rate of proliferation; this indicates a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.
Cellular integration of neural stem cell activity
The mechanisms by which the cellular metabolic program controls the proliferative activity of endogenous stem cells, such as the neural stem and progenitor cells (NSPCs) in the mammalian brain, are unknown. Sebastian Jessberger and colleagues now report a connection between
de novo
lipid biosynthesis and NSPC proliferation in the brain. Specifically, they find that fatty acid synthase is highly active during adult neurogenesis in the hippocampus. The
Spot14
gene is highly expressed in proliferating NSPCs, thereby limiting the availability of the fatty acid synthase substrate malonyl-CoA and suppressing lipidogenesis and neural differentiation.
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
1
. 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
2
, 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
3
,
4
,
5
, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA
6
, 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adult Stem Cells - metabolism
/ Animals
/ Fatty Acid Synthases - deficiency
/ Fatty Acid Synthases - genetics
/ Fatty Acid Synthases - metabolism
/ Humanities and Social Sciences
/ Labeling
/ letter
/ Lipids
/ Malonyl Coenzyme A - metabolism
/ Mice
/ Neural Stem Cells - cytology
/ Neural Stem Cells - metabolism
/ Nuclear Proteins - metabolism
/ Proteins
/ Rodents
/ Science
