Androgen receptor imprints satellite cell stemness and preserves their reservoir for lifelong regeneration and optimal repair
Abstract
Skeletal muscle stem cells (MuSC) are the guardians of muscle regeneration, sustaining tissue integrity through a delicate balance of quiescence, activation, and lineage commitment. While numerous molecular cues have been implicated in regulating these processes, the influence of androgen receptor (AR) signaling, an essential hormonal pathway for male muscle physiology, has remained largely unexplored. Here, we show that AR expression defines quiescent MuSC and acts as a safeguard of their dormancy. Integrated multiomic analyses reveal a redistribution of AR binding from quiescence-maintenance loci to regulatory elements driving activation and metabolic reprogramming during repair. Loss of AR in young adult mice disrupts this balance, precipitating premature cell-cycle entry, skewed division modalities, depletion of the stem cell reservoir, and destabilization of the niche. These defects converge with hallmarks of aging-associated androgen decline, while androgen supplementation restores regenerative competence. Together, our findings establish AR signaling as a pivotal determinant of MuSC fate and a cornerstone of skeletal muscle homeostasis.
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BibTeX
@article{rizk2026androgen,
title = {{Androgen receptor imprints satellite cell stemness and preserves their reservoir for lifelong regeneration and optimal repair}},
author = {Joe Rizk and Kamar Ghaibour and Sirine Souali-Crespo and Emilia Calvano and Aurore Bilger and Hugues Jacobs and Nadia Messaddeq and Qingshuang Cai and Erwan Grangirard and Rajesh Sahu and Arnaud Ferry and Valentin Fourcade and Joffrey Zoll and Gianni Zanardelli and Nacho Molina and Coralie Fontaine and Jean-François Arnal and Daniel Metzger and Delphine Duteil},
journal = {Science Advances},
year = {2026},
month = sep,
doi = {10.1126/sciadv.aec8073},
url = {https://univoak.hal.science/hal-05758052v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Androgen receptor imprints satellite cell stemness and preserves their reservoir for lifelong regeneration and optimal repair
AU - Joe Rizk
AU - Kamar Ghaibour
AU - Sirine Souali-Crespo
AU - Emilia Calvano
AU - Aurore Bilger
AU - Hugues Jacobs
AU - Nadia Messaddeq
AU - Qingshuang Cai
AU - Erwan Grangirard
AU - Rajesh Sahu
AU - Arnaud Ferry
AU - Valentin Fourcade
AU - Joffrey Zoll
AU - Gianni Zanardelli
AU - Nacho Molina
AU - Coralie Fontaine
AU - Jean-François Arnal
AU - Daniel Metzger
AU - Delphine Duteil
PY - 2026
DA - 2026/09/21
JO - Science Advances
DO - 10.1126/sciadv.aec8073
UR - https://univoak.hal.science/hal-05758052v1
AB - Skeletal muscle stem cells (MuSC) are the guardians of muscle regeneration, sustaining tissue integrity through a delicate balance of quiescence, activation, and lineage commitment. While numerous molecular cues have been implicated in regulating these processes, the influence of androgen receptor (AR) signaling, an essential hormonal pathway for male muscle physiology, has remained largely unexplored. Here, we show that AR expression defines quiescent MuSC and acts as a safeguard of their dormancy. Integrated multiomic analyses reveal a redistribution of AR binding from quiescence-maintenance loci to regulatory elements driving activation and metabolic reprogramming during repair. Loss of AR in young adult mice disrupts this balance, precipitating premature cell-cycle entry, skewed division modalities, depletion of the stem cell reservoir, and destabilization of the niche. These defects converge with hallmarks of aging-associated androgen decline, while androgen supplementation restores regenerative competence. Together, our findings establish AR signaling as a pivotal determinant of MuSC fate and a cornerstone of skeletal muscle homeostasis.
SN - 2375-2548
ER -