TRF2 protein found crucial for muscle stem cell identity and repair

A team from the University of Pennsylvania School of Medicine identified a new function for the telomere-protecting protein TRF2 in muscle regeneration. Normally active only at chromosome ends, TRF2 was shown to rise and fall in muscle stem cells as they move from a dormant state to active repair and back to self-renewal. Deleting the gene in mice did not kill the cells but stripped them of their stem-cell identity, causing injured muscle to accumulate adipose and fibrotic tissue.

In a mouse model of Duchenne muscular dystrophy, the absence of TRF2 hastened muscle degeneration and reduced survival. Mechanistically, TRF2 also attaches to regulatory DNA regions, especially those forming G-quadruplexes, influencing genes that preserve stem-cell characteristics. These findings may guide future therapies for muscular dystrophy and offer insight into why muscle tissue is relatively resistant to cancer. The work was funded by multiple NIH grants.