FoxO3 regulates neural stem cell homeostasis.
In the nervous system, neural stem cells (NSCs) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3(-/-) mice have fewer NSCs in vivo than wild-type counterparts. NSCs isolated from adult FoxO3(-/-) mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSCs suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSCs might have important implications for counteracting brain aging in long-lived species.
Renault
Valérie M
VM
Department of Genetics, Stanford University, CA 94305, USA.
Rafalski
Victoria A
VA
Morgan
Alex A
AA
Salih
Dervis A M
DA
Brett
Jamie O
JO
Webb
Ashley E
AE
Villeda
Saul A
SA
Thekkat
Pramod U
PU
Guillerey
Camille
C
Denko
Nicholas C
NC
Palmer
Theo D
TD
Butte
Atul J
AJ
Brunet
Anne
A
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*
D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D010100:Oxygen