FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis

被引：385

作者：

Paik, Ji-hye ^{[1
,2
,3
]}

Ding, Zhihu ^{[1
,2
,3
]}

Narurkar, Rujuta ^{[1
,2
,3
]}

Ramkissoon, Shakti ^{[4
,5
]}

Muller, Florian ^{[1
,2
,3
]}

Kamoun, Walid S. ^{[6
,7
]}

Chae, Sung-Suk ^{[6
,7
]}

Zheng, Hongwu ^{[1
,2
,3
]}

Ying, Haoqiang ^{[1
,2
,3
]}

Mahoney, Jed ^{[1
,2
,3
]}

Hiller, David ^{[8
]}

Jiang, Shan ^{[1
,2
,3
]}

Protopopov, Alexei ^{[1
,2
,3
]}

Wong, Wing H. ^{[8
]}

Chin, Lynda ^{[1
,2
,3
]}

Ligon, Keith L. ^{[4
,5
]}

DePinho, Ronald A. ^{[1
,2
,3
]}

机构：

[1] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Genet, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Boston, MA 02115 USA

[6] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA

[7] Harvard Univ, Sch Med, Boston, MA 02114 USA

[8] Stanford Univ, Dept Stat, Stanford, CA 94305 USA

来源：

CELL STEM CELL | 2009年 / 5卷 / 05期

关键词：

FORKHEAD TRANSCRIPTION FACTORS; SELF-RENEWAL; OXIDATIVE STRESS; DOWN-REGULATION; DIFFERENTIATION; PROLIFERATION; NEUROGENESIS; ASPM; EXPRESSION; FOREBRAIN;

D O I：

10.1016/j.stem.2009.09.013

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The PI3K-AKT-FoxO pathway is integral to lifespan regulation in lower organisms and essential for the stability of long-lived cells in mammals. Here, we report the impact of combined FoxO1, 3, and 4 deficiencies on mammalian brain physiology with a particular emphasis on the study of the neural stem/progenitor cell (NSC) pool. We show that the FoxO family plays a prominent role in NSC proliferation and renewal. FoxO-deficient mice show initial increased brain size and proliferation of neural progenitor cells during early postnatal life, followed by precocious significant decline in the NSC pool and accompanying neurogenesis in adult brains. Mechanistically, integrated transcriptomic, promoter, and functional analyses of FoxO-deficient NSC cultures identified direct gene targets with known links to the regulation of human brain size and the control of cellular proliferation, differentiation, and oxidative defense. Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain.

引用

页码：540 / 553

页数：14

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[1] Forkhead transcription factors contribute to execution of the mitotic programme in mammals [J].