Stem Cells on Alert: Priming Quiescent Stem Cells After Remote Injury

Rodgers et al. described a novel phase of stem cell quiescence called GAlert, which primes cells in response to injury-induced signals and requires mTORC1 activity. They found that muscle stem cells from an uninjured limb of a mouse showed a higher propensity to enter the cell cycle after injury to the opposite limb. GAlert cells were characterized by increased size, faster cell cycle entry, higher ATP content, and greater mitochondrial activity compared to quiescent cells. The study demonstrated that mTORC1 signaling is necessary and sufficient for the GAlert response, suggesting a potential circulating factor activates mTORC1 in distal stem cells. This primed state enhanced muscle regenerative capacity and was observed in other stem cell types and tissues, indicating a generalized alerting response to injury.