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

By J. T. Rodgers, K. King, Jamie O. Brett, Melinda J. Cromie, Gregory W. Charville, K. Maguire, C. Brunson, N. Mastey, Ling Liu, Chang-Ru Tsai and 2 more. Nature, 2014

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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 GAlert. 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 GAlert and that signalling through the HGF receptor cMet is also necessary. We also identify G0-to-GAlert 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 GAlert 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.

Subfields: Aging, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/97ed47f3d7d6cee42ca4a1c1431b137e9bbe1406

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Citations in the corpus

CCRK is a novel signalling hub exploitable in cancer immunotherapy (2018, background): “When a cell is presented with growth factors, cell surface receptors and signalling pathways are activated (e.g. RAS, MAPK, mTOR) (Malumbres & Barbacid, 2001; Rodgers et al., 2014), and mitogenic signals are transmitted intracellularly to drive G0-to-G1 progression.”
Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury. (2015, neutral): “’’ The transition from dormant to a primed-quiescent state (qNSC1 to qNSC2) involves the activation of protein synthesis and cell-cycle genes, which is reminiscent of the alert state of quiescentmuscle stemcellswhen exposed to a remote injury (Rodgers et al., 2014).”