Muscle stem cell adaptations to cellular and environmental stress

Skeletal Muscle

Colin Crist¹  Maria Vittoria Gugliuzza¹ 

[1] Department of Human Genetics, McGill University, 3640 University St, H3A 0C7, Montréal, Canada;Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin de la Côte Ste. Catherine, H3T 1E2, Montréal, Canada;

关键词: Muscle stem cell;    MuSC;    Stress response pathways;    Translational control of gene expression;   

DOI  :  10.1186/s13395-022-00289-6

来源: Springer

【 摘 要 】

BackgroundLifelong regeneration of the skeletal muscle is dependent on a rare population of resident skeletal muscle stem cells, also named ‘satellite cells’ for their anatomical position on the outside of the myofibre and underneath the basal lamina. Muscle stem cells maintain prolonged quiescence, but activate the myogenic programme and the cell cycle in response to injury to expand a population of myogenic progenitors required to regenerate muscle. The skeletal muscle does not regenerate in the absence of muscle stem cells.Main bodyThe notion that lifelong regeneration of the muscle is dependent on a rare, non-redundant population of stem cells seems contradictory to accumulating evidence that muscle stem cells have activated multiple stress response pathways. For example, muscle stem cell quiescence is mediated in part by the eIF2α arm of the integrated stress response and by negative regulators of mTORC1, two translational control pathways that downregulate protein synthesis in response to stress. Muscle stem cells also activate pathways to protect against DNA damage, heat shock, and environmental stress. Here, we review accumulating evidence that muscle stem cells encounter stress during their prolonged quiescence and their activation. While stress response pathways are classically described to be bimodal whereby a threshold dictates cell survival versus cell death responses to stress, we review evidence that muscle stem cells additionally respond to stress by spontaneous activation and fusion to myofibres.ConclusionWe propose a cellular stress test model whereby the prolonged state of quiescence and the microenvironment serve as selective pressures to maintain muscle stem cell fitness, to safeguard the lifelong regeneration of the muscle. Fit muscle stem cells that maintain robust stress responses are permitted to maintain the muscle stem cell pool. Unfit muscle stem cells are depleted from the pool first by spontaneous activation, or in the case of severe stress, by activating cell death or senescence pathways.

【 授权许可】

CC BY