Dynamic increases in p53 expression suppress human myoblast differentiation

Abstract

Skeletal muscle maintenance and regeneration are highly regulated by cell fate decisions made by muscle stem cells and their progeny, myoblasts. Although the transcription factor p53 is well known for its role in cellular stress responses, cell cycle regulation, and tumor prevention, emerging evidence suggests that p53 also plays a critical role in determining whether myoblasts differentiate into muscle fibers or remain single cells that re-enter quiescence to replenish the satellite cell pool. Most previous studies, however, have relied on static, population-level measurements of p53, leaving its dynamic real-time behavior in individual myoblasts largely unexplored. In this study, we use single cell time-lapse microscopy to investigate temporal patterns of p53 activity in fluorescently-tagged immortalized human myoblasts induced to differentiate. We find that cells in which p53 levels increase more quickly and accumulate to higher amplitudes tend to remain single cells rather than differentiate and fuse into myofibers. Understanding how p53 dynamics influence muscle cell fate may provide fundamental insights into muscle maintenance, regeneration, and degenerative disease.