FoxO3 Regulates Neural Stem Cell Homeostasis

被引：473

作者：

Renault, Valerie M. ^{[1
]}

Rafalski, Victoria A. ^{[1
,2
]}

Morgan, Alex A. ^{[3
,6
,7
]}

Salih, Dervis A. M. ^{[1
]}

Brett, Jamie O. ^{[1
]}

Webb, Ashley E. ^{[1
]}

Villeda, Saul A. ^{[1
,2
]}

Thekkat, Pramod U. ^{[1
]}

Guillerey, Camille ^{[1
]}

Denko, Nicholas C. ^{[4
]}

Palmer, Theo D. ^{[5
]}

Bufte, Atul J. ^{[3
,6
,7
]}

Brunet, Anne ^{[1
,2
]}

机构：

[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[2] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA

[3] Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA

[6] Stanford Univ, Lucile Packard Childrens Hosp, Dept Pediat, Stanford, CA 94304 USA

[7] Stanford Univ, Lucile Packard Childrens Hosp, Dept Med, Stanford, CA 94304 USA

来源：

CELL STEM CELL | 2009年 / 5卷 / 05期

关键词：

SELF-RENEWAL; VASCULAR NICHE; DENTATE GYRUS; NEUROGENESIS; PROLIFERATION; PTEN; DIFFERENTIATION; SURVIVAL; HYPOXIA; MAINTENANCE;

D O I：

10.1016/j.stem.2009.09.014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：527 / 539

页数：13

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