Gene expression profiling reveals a novel mechanism regulating adult neurogenesis

Mechanisms controlling the proliferative activity of hippocampal neural stem cells (NSCs) play a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSC activity remains unknown. Here we show that Spot14, previously implicated in cancer and hepatic lipid metabolism, is highly enriched in a relatively quiescent hippocampal NSC population in vitro and in vivo. Spot14 lowers the availability of malonyl-CoA, which is an essential substrate of fatty acid synthase (FASN), the key enzyme of de novo lipogenesis. We show that lipid synthesis is a highly active metabolic process in dividing NSCs and that conditional deletion of FASN in adult NSCs reduces neurogenesis, indicating that levels of lipid synthesis are associated with NSC proliferation. Thus, we here identified a functional coupling between regulation of lipid metabolism and NSC proliferation, connecting cellular metabolism with NSC homeostasis in the adult brain.

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