Publication Date:
2014-05-30
Description:
A unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state. 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. 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, G0 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 G0 into G(Alert) and that signalling through the HGF receptor cMet is also necessary. We also identify G0-to-G(Alert) transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into G(Alert) 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065227/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065227/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rodgers, Joseph T -- King, Katherine Y -- Brett, Jamie O -- Cromie, Melinda J -- Charville, Gregory W -- Maguire, Katie K -- Brunson, Christopher -- Mastey, Namrata -- Liu, Ling -- Tsai, Chang-Ru -- Goodell, Margaret A -- Rando, Thomas A -- F30 AG035521/AG/NIA NIH HHS/ -- I01 BX002324/BX/BLRD VA/ -- K08 HL098898/HL/NHLBI NIH HHS/ -- P01 AG036695/AG/NIA NIH HHS/ -- R01 AG023806/AG/NIA NIH HHS/ -- R01 AG047820/AG/NIA NIH HHS/ -- R01 AG23806/AG/NIA NIH HHS/ -- R01 AR062185/AR/NIAMS NIH HHS/ -- R01 DK092883/DK/NIDDK NIH HHS/ -- R37 AG023806/AG/NIA NIH HHS/ -- England -- Nature. 2014 Jun 19;510(7505):393-6. doi: 10.1038/nature13255. Epub 2014 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Paul F. Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Pediatrics and Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Paul F. Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA [3] Neurology Service and Rehabilitation Research and Development Center of Excellence, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870234" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Cycle/genetics/*physiology
;
Cells, Cultured
;
G0 Phase/genetics/*physiology
;
Gene Expression Profiling
;
Gene Expression Regulation
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Multiprotein Complexes/genetics/*metabolism
;
Muscle, Skeletal/*cytology/injuries/metabolism
;
Regeneration/physiology
;
Satellite Cells, Skeletal Muscle/*cytology/metabolism
;
TOR Serine-Threonine Kinases/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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