Continuous Large Maf Activity Maintains Fast Myofiber Identity and Multicellular Homeostasis in Adult Skeletal Muscle
- 1University of Tsukuba
Abstract
Fast myofibers are preferentially affected during aging, exhibiting atrophy and shifts toward slower myofiber programs, yet the mechanisms preserving established fast-fiber identity remain unclear. Here, we show that the large Maf transcription factors Mafa, Mafb, and Maf are continuously required to maintain type IIb myofiber identity in adult skeletal muscle. Inducible deletion of large Mafs caused near-complete loss of type IIb fibers, a transition toward type IIx/IIa states, reduced strength, and increased fatigue resistance. RNA-seq and ATAC-seq revealed transcriptional and chromatin accessibility remodeling across the fast myosin locus, characterized by persistent loss of Myh4 expression and increased accessibility around Myh1. Single-nucleus RNA-seq identified transient myonuclei co-expressing multiple myosin isoforms before emergence of a Myh1-dominant state, accompanied by remodeling of non-myonuclear cell populations. These changes shared features with aging- and denervation-associated muscle remodeling. Thus, continuous large Maf activity maintains adult fast myofiber identity and coordinates skeletal muscle tissue homeostasis.
Related
- Snurportin-1 maintains muscle niche integrity and myogenic progenitor homeostasis
- Genetic coupling of hydathode formation with leaf morphogenesis maintains water homeostasis
- TMEM55B Maintains Lysosomal Homeostasis and Promotes ER–Lysosome Calcium Signaling
- A tonic PDGFA-dependent niche organizer maintains alveolar homeostasis
- The bHLH121-CAT2 module maintains root tip redox homeostasis to confer salt tolerance additively with the SOS pathway in Arabidopsis
BibTeX
@misc{sadaki2026continuous,
title = {{Continuous Large Maf Activity Maintains Fast Myofiber Identity and Multicellular Homeostasis in Adult Skeletal Muscle}},
author = {S. Sadaki and R. Tsuji and T. Matsumoto and T. Hayashi and T. Sugasawa and N. Horii and K.-i. Yasunaga and E. Jauliac and T. Kudo and Y. Ono and P. Maire and S. Takahashi and R. Fujita},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.758120},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.758120v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Continuous Large Maf Activity Maintains Fast Myofiber Identity and Multicellular Homeostasis in Adult Skeletal Muscle
AU - S. Sadaki
AU - R. Tsuji
AU - T. Matsumoto
AU - T. Hayashi
AU - T. Sugasawa
AU - N. Horii
AU - K.-i. Yasunaga
AU - E. Jauliac
AU - T. Kudo
AU - Y. Ono
AU - P. Maire
AU - S. Takahashi
AU - R. Fujita
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.758120
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.758120v1
AB - Fast myofibers are preferentially affected during aging, exhibiting atrophy and shifts toward slower myofiber programs, yet the mechanisms preserving established fast-fiber identity remain unclear. Here, we show that the large Maf transcription factors Mafa, Mafb, and Maf are continuously required to maintain type IIb myofiber identity in adult skeletal muscle. Inducible deletion of large Mafs caused near-complete loss of type IIb fibers, a transition toward type IIx/IIa states, reduced strength, and increased fatigue resistance. RNA-seq and ATAC-seq revealed transcriptional and chromatin accessibility remodeling across the fast myosin locus, characterized by persistent loss of Myh4 expression and increased accessibility around Myh1. Single-nucleus RNA-seq identified transient myonuclei co-expressing multiple myosin isoforms before emergence of a Myh1-dominant state, accompanied by remodeling of non-myonuclear cell populations. These changes shared features with aging- and denervation-associated muscle remodeling. Thus, continuous large Maf activity maintains adult fast myofiber identity and coordinates skeletal muscle tissue homeostasis.
ER -