Myonuclear Dynamics After Skeletal Muscle Surgical Injury

A hallmark of damaged skeletal muscle fibers is displaced myonuclei that are no longer peripherally positioned. Displaced myonuclei are dogmatically thought to be derived exclusively from muscle stem cell (satellite cell) fusion. Using a surgical resection muscle injury model and in vivo recombination-independent "resident" (nonsatellite cell-derived) myonuclear labeling, we detail the prevalence, time course, and origin of displaced myonuclei in response to a nonchemically-mediated muscle trauma. We found that: (1) nonsatellite cell-derived (resident) displaced myonuclei emerge 7 days after surgical injury in similar proportion to exogenous (satellite cell-derived) displaced myonuclei, with a biased prevalence in myosin heavy chain IIB muscle fibers, (2) muscle fibers with multiple (≥ 2) displaced resident myonuclei in cross-section were an unexpected but noteworthy feature of muscle fibers 7 days after injury, (3) embryonic myosin-expressing fibers at 7 days postsurgery expectedly contain predominantly satellite cell-derived displaced myonuclei, but a subset have displaced resident myonuclei, and (4) satellite cell numbers in intact muscle do not increase until 7 days postsurgery. These data may help inform whether to target satellite cell-initiated processes, myonuclear-initiated processes, or both to facilitate muscle fiber injury repair. This information could lead to more effective therapeutic strategies for treating muscle trauma.