Molecular Regulation of Satellite Cell Fate

Abstract

Muscle homeostasis and regeneration are complex cellular processes orchestrated by muscle stem cells and their interaction with their stem cell microenvironment. The fate of a muscle stem cell is influenced by different conditions such as muscle injury, cold stress, or disease. During extensive muscle repair and in the context of muscular dystrophy, we identified the critical function of the Epidermal Growth Factor Receptor (EGFR) in establishing cell polarity and in turn the efficient formation of myogenic progeny able to repair muscle. Using a novel drug screen, we identified the p53 protein to regulate muscle stem cell fate decision to repress the formation of brown adipose tissue as a means to regulate whole-body metabolism. To increase the impact of our research we also optimized protocols evaluating mouse satellite cell transplantation to delineate stem cell hierarchy and developed a new paradigm to model human muscle stem cell fate to better translate our findings into the clinical arena. These findings reveal the tunable nature of stem cell fate decisions and highlight the development of research tools to accelerate the translation of research findings to improve human health.