Elucidating the switch molecule in muscle stem cells that initiates muscle formation

Tsukuba, Japan—Japan's aging population urgently needs methods to prevent musculoskeletal diseases. Skeletal muscles, which are essential for physical activity, deteriorate in both volume and function with age, reducing the quality of life. To counteract muscle aging and preserve muscle regeneration capabilities, the pivotal role of stem cells, particularly skeletal muscle stem cells, in muscle tissue must be understood.

Under normal conditions, adult skeletal muscle stem cells remain dormant. They are activated and multiply in response to muscle damage to facilitate repair and regeneration. Delays or abnormalities in this process can disrupt muscle regeneration, accelerating muscle aging. This research team has been investigating the factors that activate and stimulate the proliferation of skeletal muscle stem cells and those that induce the transition of these proliferating cells to the muscle differentiation stage.

In this study, researchers used mice capable of distinguishing the activation state of skeletal muscle stem cells to analyze gene expression during the quiescent, proliferative, and differentiated phases. Analysis of the mice revealed that DUSP13 and DUSP27 act as switches, inducing proliferating skeletal muscle stem cells into the differentiation stage. Furthermore, these enzymes are directly regulated by the muscle differentiation regulator MYOD. Mice lacking the genes for these enzymes exhibited delayed muscle regeneration owing to a malfunction in the muscle differentiation switch. The findings of this study can potentially contribute to the development of drugs for treating muscle weakness and muscle mass loss that are characteristic of sarcopenia.

###
This work was supported by grants from the MEXT Leading Initiative for Excellent Young Researchers (R.F.), Grant-in-Aid for Early-Career Scientists (21K17679; R.F.), and Grant-in-Aid for Scientific Research (B) (24K02876; R.F.) from the Japan Society for the Promotion of Science (JSPS). This research was also supported by AMED-CREST (JP23gm171008h). This work was also supported, in part, by grants to R.F. from the Takeda Science Foundation and Mochida Memorial Foundation for Medical and Pharmaceutical Research. Furthermore, this work received support from the Grant-in-Aid for the Japan Aerospace Exploration Agency (14YPTK-407 005512; S.T.) and the Grant-in-Aid for Scientific Research on Innovative Area from MEXT (18H04965; S.T.). T.H. and S.S were funded by JSPS Research Fellowships for Young Scientists (22J10954 [T.H.] and 23KJ0287 [S.S.]).

_{Original Paper}

Title of original paper:
Dual-specificity phosphatases 13 and 27 as key switches in muscle stem cell transition from proliferation to differentiation

Journal:
Stem Cells

DOI:
10.1093/stmcls/sxae045

_{Correspondence}

Assistant Professor FUJUTA, Ryo
Division of Regenerative Medicine, Transborder Medical Research Center / Institute of Medicine, University of Tsukuba

Professor TAKAHASHI, Satoru
Division of GM Mouse Resources, Transborder Medical Research Center / Institute of Medicine, University of Tsukuba

_{Related Link}

Transborder Medical Research Center

Institute of Medicine