TRF2 couples muscle stem cell identity to regenerative repair.

Authors

Ji-Hyung Lee, Kiran Kumar Nakka, Ryan P Calhoun, Sarah Hachmer, Adity Gupta, Eric Arreza, Lynn A Megeney, Patrick Seale, Roger A Greenberg, F Jeffrey Dilworth, Foteini Mourkioti

Published in

Science advances. Volume 12. Issue 31. Pages eaei7316. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Stem cell-mediated regeneration is essential for tissue integrity. In skeletal muscle, tissue repair largely depends on muscle stem cells (MuSCs), which undergo dynamic cell-state transitions through making precise fate decisions during regeneration. However, the molecular regulators of cell-state conversion in MuSCs remain unclear. Here, we identify a previously unrecognized, noncanonical role for TRF2 in MuSC biology. TRF2 is dynamically regulated upon injury and required to preserve stem cell identity, support reparative myogenesis, and sustain self-renewal. MuSC-specific TRF2 disruption exacerbates muscular dystrophy pathology in mice, recapitulating key features of human disease. Mechanistically, TRF2 associates with regulatory regions enriched for DNA G-quadruplex-forming sequences at lineage-specific genes, sustaining their expression. These findings establish TRF2 as a pivotal regulator of adult stem cell function and tissue-specific regenerative responses.

PMID:
42536731
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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