TRF2 protein preserves muscle stem cell identity, aiding repair

Researchers at the Perelman School of Medicine, University of Pennsylvania discovered that the telomere‑capping protein TRF2 has a dual role in skeletal muscle. Beyond protecting chromosome ends, TRF2 acts as a genome‑wide transcriptional regulator that dynamically fluctuates as muscle stem cells transition between quiescence, activation, proliferation and self‑renewal. When TRF2 is removed in mouse models, the stem cells do not die but lose their lineage identity, leading to impaired regeneration, fibrosis and fat infiltration instead of healthy muscle.

In mice carrying a Duchenne muscular dystrophy (DMD) mutation, loss of TRF2 accelerates muscle degeneration, increases fibrosis and shortens survival, highlighting its potential as a therapeutic target for muscular dystrophies and offering insight into why skeletal muscle resists tumor formation.