Findings establish TRF2 as a pivotal regulator of adult stem cell function and tissue-specific regenerative responses and establish TRF2 as a pivotal regulator of adult stem cell function and tissue-specific regenerative responses.
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.
Muscle stem cells (MuSCs) represent a subset of satellite cells (SCs) and constitute the stem cell compartment of the skeletal muscle tissue. MuSCs and SCs are quiescent under homeostatic conditions but activate upon injury to drive regeneration and repopulation of the stem cell pool. Heterogeneity has become a central...
O. Ashekyan, Marie J. Catenacci, Corentin Guilhot et al.· Frontiers in Cell and Develo...· 0 citations
It is established that PAX3-SIX2 expression correlates with distinct MuSCs behavior, influencing regeneration rates in a muscle-type-dependent context, and it is suggested that PAX3-SIX2 heterogeneity could be leveraged for targeted therapeutic strategies in muscle-wasting diseases.
Virginia Zoglio, Sarah Chebouti, Fayez Issa et al.· Science Advances· 0 citations
The current knowledge and recent advances on how this sensory organelle controls muscle stem cell quiescence, enables mechano-sensation, and regulates activation following tissue injury and during asymmetric self-renewal are synthesized.
Anna Rausch de Traubenberg, Ludivine Rotard, Caroline E. Brun· Stem Cell Reviews and Report...· 0 citations
Molecular, cellular, and niche-level evidence across these settings are integrated to explain why FGF signaling produces divergent outcomes and to clarify how cellular context and timing should inform therapeutic modulation.
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...
Ingrid R. Aragon, Neha Patole, Ajay Vachanaram et al.· Frontiers in Cell and Develo...· 0 citations
ABSTRACT Skeletal muscle aging is increasingly recognized as a failure of tissue‐level coordination rather than a consequence of isolated defects in individual cell types. Recent advances in single‐cell, spatial, and multimodal omics have revealed that aging remodels the abundance, functional states, and interactions o...
Seongwan Kim, M. Kim, Yong Ryoul Yang· Aging Cell· 0 citations
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