NFATc1 balances quiescence and proliferation of skin stem cells

被引：422

作者：

Horsley, Valerie ^{[1
]}

Aliprantis, Antonios O. ^{[2
,3
,4
]}

Polak, Lisa ^{[1
]}

Glimcher, Laurie H. ^{[2
,3
,4
]}

Fuchs, Elaine ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Mammalian Cell Biol & Dev, Howard Hughes Med Inst, New York, NY 10065 USA

[2] Harvard Univ, Sch Publ Hlth, Dept Infect Dis & Immunol, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA USA

来源：

CELL | 2008年 / 132卷 / 02期

关键词：

D O I：

10.1016/j.cell.2007.11.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Quiescent adult stem cells reside in specialized niches where they become activated to proliferate and differentiate during tissue homeostasis and injury. How stem cell quiescence is governed is poorly understood. We report here that NFATc1 is preferentially expressed by hair follicle stem cells in their niche, where its expression is activated by BMP signaling upstream and it acts downstream to transcriptionally repress CDK4 and maintain stem cell quiescence. As stem cells become activated during hair growth, NFATc1 is downregulated, relieving CDK4 repression and activating proliferation. When calcineurin/NFATc1 signaling is suppressed, pharmacologically or via complete or conditional NFATc1 gene ablation, stem cells are activated prematurely, resulting in precocious follicular growth. Our findings may explain why patients receiving cyclosporine A for immunosuppressive therapy display excessive hair growth, and unveil a functional role for calcium-NFATc1-CDK4 circuitry in governing stem cell quiescence.

引用

页码：299 / 310

页数：12

共 62 条

[1]

Activation and cellular localization of the cyclosporine A-sensitive transcription factor NF-AT in skeletal muscle cells [J].