Dual-specificity phosphatases 13 and 27 as key switches in muscle stem cell transition from proliferation to differentiation

Abstract

SummaryMuscle regeneration depends on muscle stem cell (MuSCs) activity. These cells are typically quiescent but become activated upon muscle injury, transitioning from proliferation to differentiation. Myogenic regulatory factors, including myoblast determination protein 1 (MyoD), regulate the fate transition of MuSCs. However, the role of MYOD in this process is not yet clear. Using previously established MyoD knock-in (MyoD-KI) mice, we revealed that MyoD targets dual-specificity phosphatase (Dusp) 13 and Dusp27. InDusp13:Dusp27double knock-out (DKO) mice, the ability for muscle regeneration after injury was found to be reduced. Moreover, single-cell RNA sequencing of MyoD-high expressing MuSCs from MyoD-KI mice revealed thatDusp13andDusp27are only expressed in specific populations within MyoD-high MuSCs, which also expressMyogenin. OverexpressingDusp13in 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.