Tracking Satellite Cell Dynamics During Skeletal Muscle Plasticity

To characterize a newly developed genetic mouse model for tracking satellite cell dynamics during skeletal muscle adaptation, disease and aging. Once characterized, the Pax7-THG mouse will be made freely available to all NSMRC members and the research community at large. Background: Satellite cells are the primary stem cell in adult skeletal muscle. There is a broad consensus within the field that satellite cells are absolutely required for skeletal muscle maturation during post-natal development and muscle regeneration following injury. In contrast, there remains conflicting and incomplete knowledge regarding the exact role of satellite cells in adult skeletal muscle adaptation to changes in contractile activity, certain myopathies and maintenance with aging. As such, it is difficult to rigorously assess the rehabilitative potential of satellite cells to restore the loss of muscle mass and function as the result of inactivity, injury, disease and/or aging. A major hurdle to defining the role of satellite cells under these different conditions has been the inability to track their behavior in vivo; in particular, it has been experimentally impossible to quantitatively track satellite cells following fusion into the muscle syncytium because of translocation of the label to native myonuclei. To address this fundamental gap in our knowledge, we have developed a new, inducible mouse strain that enables the permanent labeling of satellite cell nuclei in adult skeletal muscle. The Pax7-THG mouse enables us to specifically track satellite cell abundance and fusion into mature myofibers. This novel mouse strains will allow us to definitively answer fundamental questions related to the role of satellite cells in adult skeletal muscle including: • Is DNA replication obligatory for satellite cell fusion to a myofiber? • Does satellite cell fusion occur prior to myofiber growth? • Are centrally located nuclei derived from satellite cells? For this initial pilot study, we will use the synergist ablation model of skeletal muscle hypertrophy to assess the ability of the Pax7-THG mouse to track satellite cell abundance and dynamics given the robust proliferation and fusion of satellite cells that occur with this model.