Androgen receptor imprints satellite cell stemness and preserves their reservoir for lifelong regeneration and optimal repair
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.
Authors
- Nadia Messaddeq (ORCID: https://orcid.org/0000-0001-8398-6415)
- Joffrey Zoll (ORCID: https://orcid.org/0009-0006-0090-1484)
- Kamar Ghaibour
- Coralie Fontaine (ORCID: https://orcid.org/0000-0002-7253-922X)
- Jean‐François Arnal (ORCID: https://orcid.org/0000-0003-2229-6300)
- Erwan Grandgirard (ORCID: https://orcid.org/0000-0002-5263-2144)
- Nacho Molina (ORCID: https://orcid.org/0000-0003-0233-3055)
- Arnaud Ferry (ORCID: https://orcid.org/0000-0002-6050-4556)
- Qingshuang Cai (ORCID: https://orcid.org/0000-0002-6107-6477)
- Delphine Duteil (ORCID: https://orcid.org/0000-0001-5826-0153)
- Sirine Souali‐Crespo (ORCID: https://orcid.org/0009-0003-0881-640X)
- J. Rizk (ORCID: https://orcid.org/0009-0005-5703-5401)
- Rajesh Sahu (ORCID: https://orcid.org/0000-0002-8231-9132)
- Hugues Jacobs
- Emilia Calvano
- Gianni Zanardelli
- Daniel METZGER (ORCID: https://orcid.org/0000-0002-5555-046X)
- Aurore Bilger (ORCID: https://orcid.org/0009-0005-7781-4154)
- Valentin Fourcade (ORCID: https://orcid.org/0009-0001-1972-8777)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Sorbonne Université (FR)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Institut de Myologie (FR)
- Institut des Maladies Métaboliques et Cardiovasculaires (FR)
- Centre de Recherche en Myologie
- Université de Strasbourg (FR)
Publication Details
- Journal
- Science Advances
- Published
- 2026-09-09
- DOI
- https://doi.org/10.1126/sciadv.aec8073
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00