mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert

被引:543
作者
Rodgers, Joseph T. [1 ,2 ]
King, Katherine Y. [3 ,4 ]
Brett, Jamie O. [1 ,2 ]
Cromie, Melinda J. [1 ,2 ]
Charville, Gregory W. [1 ,2 ]
Maguire, Katie K. [1 ,2 ]
Brunson, Christopher [1 ,2 ]
Mastey, Namrata [1 ,2 ]
Liu, Ling [1 ,2 ]
Tsai, Chang-Ru [3 ,4 ]
Goodell, Margaret A. [3 ,4 ]
Rando, Thomas A. [1 ,2 ,5 ,6 ]
机构
[1] Stanford Univ, Sch Med, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
[3] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
[4] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA
[5] Vet Affairs Palo Alto Hlth Care Syst, Neurol Serv, Palo Alto, CA 94304 USA
[6] Vet Affairs Palo Alto Hlth Care Syst, Rehabil Res & Dev Ctr Excellence, Palo Alto, CA 94304 USA
基金
美国国家卫生研究院;
关键词
HEPATOCYTE GROWTH-FACTOR; SKELETAL-MUSCLE; MOLECULAR REGULATION; EXPRESSION DATA; REGENERATION; PROGENITORS; RENEWAL; EVENTS; SYSTEM; INJURY;
D O I
10.1038/nature13255
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state(1). Although quiescence serves an essential role in preserving stem cell function until the stem cell is needed in tissue homeostasis or repair, defects in quiescence can lead to an impairment in tissue function(2). The extent to which stem cells can regulate quiescence is unknown. Here we show that the stem cell quiescent state is composed of two distinct functional phases, G(0) and an 'alert' phase we term G(Alert). Stem cells actively and reversibly transition between these phases in response to injury-induced systemic signals. Using genetic mouse models specific to muscle stem cells (or satellite cells), we show that mTORC1 activity is necessary and sufficient for the transition of satellite cells from G(0) into G(Alert) and that signalling through the HGF receptor cMet is also necessary. We also identify G(0)-to-G(Alert) transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into GAlert possess enhanced tissue regenerative function. We propose that the transition of quiescent stem cells into G(Alert) functions as an 'alerting' mechanism, an adaptive response that positions stem cells to respond rapidly under conditions of injury and stress, priming them for cell cycle entry.
引用
收藏
页码:393 / +
页数:15
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