1. Dual-specificity phosphatases 13 and 27 as key switches in muscle stem cell transition from proliferation to differentiation
- Author
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Hayashi, Takuto, Sadaki, Shunya, Tsuji, Ryosuke, Okada, Risa, Fuseya, Sayaka, Kanai, Maho, Nakamura, Ayano, Okamura, Yui, Muratani, Masafumi, Wenchao, Gu, Sugasawa, Takehito, Mizuno, Seiya, Warabi, Eiji, Kudo, Takashi, Takahashi, Satoru, and Fujita, Ryo
- Abstract
Muscle regeneration depends on muscle stem cell (MuSC) activity. Myogenic regulatory factors, including myoblast determination protein 1 (MyoD), regulate the fate transition of MuSCs. However, the direct target of MYOD in the process is not completely clear. Using previously established MyoD knock-in (MyoD-KI) mice, we revealed that MyoD targets dual-specificity phosphatase (Dusp) 13 and Dusp27. In Dusp13:Dusp27double knock-out mice, the ability for muscle regeneration after injury was reduced. Moreover, single-cell RNA sequencing of MyoD-high expressing MuSCs from MyoD-KI mice revealed that Dusp13and Dusp27are expressed only in specific populations within MyoD-high MuSCs, which also express Myogenin. Overexpressing Dusp13in MuSCs causes premature muscle differentiation. Thus, we propose a model where DUSP13 and DUSP27 contribute to the fate transition of MuSCs from proliferation to differentiation during myogenesis.Graphical Abstract
- Published
- 2024
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