Impacts of hypoxia and hypoxia-induced factors on skeletal muscle repair and muscle stem cells

项目摘要

PROJECT ABSTRACT   Skeletal muscle plays a pivotal role in locomotion and metabolism. Improper function of skeletal muscle, as seen in conditions such as degenerative myopathies and sarcopenia, has profound impacts on human health. Reversely, many human diseases, such as heart failure, chronic obstructive pulmonary disease and type 2 diabetes, cause impairment of skeletal muscle function. To break the vicious cycle, it is important to understand the molecular mechanisms underlying skeletal muscle repair. Skeletal muscle stem cells (also called satellite cells) serve as an important reservoir of myogenic cells that have the potential to accrete to, repair or even rejuvenate skeletal muscle fibers. The life-long maintenance of this potential relies on orchestrated satellite cell behaviors involving intricate balances between proliferation, differentiation and self- renewal. Accumulating evidence indicate that low oxygen tension (hypoxia) is a physiological stem cell niche factor that regulates stem cell behaviors. However, little is known about the impact of hypoxia and hypoxia- induced signaling on satellite cells and skeletal muscle repair. In the present study, we will 1) identify key factors that mediate the hypoxia signaling in satellite cells; 2) investigate key regulators that modulate satellite cell responses to hypoxia; and 3) explore novel therapeutic approaches that may improve skeletal muscle repair in physiological and human disease-relevant conditions. We expect results from this study will substantially contribute to the understanding of satellite cells and skeletal muscle repair, and also shed light on interventions for improving skeletal muscle health.