Project Summary Rotator cuff tears are an extremely common cause of shoulder pain and disability. Up to 50% of patients greater than the age of 65 years of age have evidence of a rotator cuff tear. In addition, patients with small asymptomatic cuff tears tend to progress to larger, symptomatic tears. The outcomes of surgical repair of small cuff tears are good, but there has been limited success in the surgical treatment in the surgical treatment of massive cuff tears. Massive cuff tears have been linked with fatty infiltration of the rotator cuff muscles. Patients with large cuff tears who develop fatty infiltration have poorer clinical outcomes and higher rates of failure after attempted repair. We have previously found that a newly discovered stem cell population-FAPs-is critical in the development of fatty infiltration after cuff injury. Further, these cells share similar expression patterns with the beige adipocyte lineage, a distinct cell population that has unique thermogenic and metabolic capabilities that could improve muscle function. This study will support Steven Garcia, MD, a post doctoral resident in the UCSF Department of Orthopedic Surgery. He will use our well-studied animal model and a novel repair model to evaluate the mechanism by which FAP cells can improve muscle function through differentiation into a beige fat phenotype. Understanding the relationship between FAP cells and beige adipocytes and utilizing these cells in endogenous and exogenous treatment strategies could help improve muscle quality in cuff repair as well as other muscle injury states.