期刊
NATURE
卷 510, 期 7505, 页码 393-+出版社
NATURE PORTFOLIO
DOI: 10.1038/nature13255
关键词
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资金
- Glenn Foundation for Medical Research
- Department of Veterans Affairs
- National Institutes of Health [K99 AG041764, K08 HL098898, R01 DK092883, P01 AG036695, R01 AG23806, R01 AR062185]
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.
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