AMPKα2 is a skeletal muscle stem cell intrinsic regulator of myonuclear accretion

Kneppers, A. E. M.; Theret, M.; Ben Larbi, S.; Gsaier, L.; Saugues, A.; Dabadie, C.; Ferry, A.; Sakamoto, K.; Mounier, R.

doi:10.1101/2022.11.02.514556

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bioRxiv · 10.1101/2022.11.02.514556

AMPKα2 is a skeletal muscle stem cell intrinsic regulator of myonuclear accretion

Kneppers, A. E. M.·Theret, M.·Ben Larbi, S.·Gsaier, L.·Saugues, A.·Dabadie, C.·Ferry, A.·Sakamoto, K.·Mounier, R.

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Abstract

Due to the post-mitotic nature of skeletal muscle fibers, adult muscle maintenance relies on dedicated muscle stem cells (MuSCs). In most physiological contexts, MuSCs support myofiber homeostasis by contributing to myonuclear accretion, which requires a coordination of cell-type specific events between the myofiber and MuSCs. Here, we addressed the role of the kinase AMPK2 in the coordination of these events supporting myonuclear accretion. We demonstrate that AMPK2 deletion impairs skeletal muscle regeneration. Through in vitro assessments of MuSC myogenic fate and EdU-based cell tracing, we reveal a MuSC-specific role of AMPK2 in the regulation of myonuclear accretion, which is mediated by phosphorylation of the non-metabolic substrate BAIAP2. Similar cell tracing in vivo shows that AMPK2 knockout mice have a lower rate of myonuclear accretion during regeneration, and that MuSC-specific AMPK2 deletion decreases myonuclear accretion in response to myofiber contraction. Together, this demonstrates that AMPK2 is a MuSC-intrinsic regulator of myonuclear accretion.

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Kneppers, A. E. M., Theret, M., Ben Larbi, S., Gsaier, L., Saugues, A., Dabadie, C., Ferry, A., Sakamoto, K., Mounier, R.. 2022-11-02. AMPKα2 is a skeletal muscle stem cell intrinsic regulator of myonuclear accretion. https://doi.org/10.1101/2022.11.02.514556

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