NRSA Fellowship for Davis Englund: Determining the Fiber Type-Specific Requirements for Satellite Cells During Skeletal Muscle Hypertrophy

Developing interventional strategies that increase skeletal muscle mass are critical for the restoration of whole body health and function in several clinical populations afflicted by skeletal muscle wasting. A s stem cell-based therapies have been efficacious treatment strategies for a certain degenerative diseases, the use of muscle stem cells (satellite cells) to treat the loss of muscle mass is considered to be a promising therapeutic strategy. Work from our lab demonstrates that while reduced satellite cell content does not influence muscle growth at the onset of a hypertrophic stimulus, satellite cell mediated myonuclear accretion is required to support long- term muscle growth. The mechanism precipitating a shift in the requirement for satellite cell activation and myonuclear addition during sustained muscle growth is unknown. Moreover, our understanding for satellite cell-mediated muscle growth is currently restricted to the plantaris muscle, which is comprised exclusively of type 2 (fast twitch) muscle fibers. Emerging evidence has made it clear these findings may not extend to type 1 (slow twitch) fibers, a fiber type that comprises ~50% of human skeletal muscle and is known to positively influence metabolism and health. The proposed study addresses these fundamental gaps in our knowledge and will provide critical information necessary to develop and evaluate future satellite cell-based treatment strategies. My overarching hypothesis is that satellite cell fusion is required for growth in type 1 fibers, whereas type 2 fibers activate compensatory mechanisms to support growth in the absence of myonuclear addition.