AMPKα2 is a skeletal muscle stem cell intrinsic regulator of myonuclear accretion
Anita Kneppers,
Sabrina Ben Larbi,
Marine Theret,
Audrey Saugues,
Carole Dabadie,
Linda Gsaier,
Arnaud Ferry,
Philipp Rhein,
Julien Gondin,
Kei Sakamoto,
Rémi Mounier
Affiliations
Anita Kneppers
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France
Sabrina Ben Larbi
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France
Marine Theret
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France
Audrey Saugues
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France
Carole Dabadie
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France
Linda Gsaier
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France
Arnaud Ferry
Myology Center of Research, Association of Myology Institute, INSERM UMRS974, Sorbonne Université, Paris, France; Université Paris Cité, Paris, France
Philipp Rhein
Nestlé Research, Société des Produits Nestlé S.A., EPFL Innovation Park, Lausanne, Switzerland; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), EPFL Innovation Park, Lausanne, Switzerland
Julien Gondin
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France
Kei Sakamoto
Nestlé Research, Société des Produits Nestlé S.A., EPFL Innovation Park, Lausanne, Switzerland; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Rémi Mounier
Institut NeuroMyoGène, CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, Lyon, France; Corresponding author
Summary: 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 AMPKα2 in the coordination of these events supporting myonuclear accretion. We demonstrate that AMPKα2 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 AMPKα2 in the regulation of myonuclear accretion, which is mediated by phosphorylation of the non-metabolic substrate BAIAP2. Similar cell tracing in vivo shows that AMPKα2 knockout mice have a lower rate of myonuclear accretion during regeneration, and that MuSC-specific AMPKα2 deletion decreases myonuclear accretion in response to myofiber contraction. Together, this demonstrates that AMPKα2 is a MuSC-intrinsic regulator of myonuclear accretion.