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:Dusp27 double 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 Dusp13 and Dusp27 are expressed only in specific populations within MyoD-high MuSCs, which also express Myogenin. Overexpressing Dusp13 in 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.
摘要:
肌肉再生取决于肌肉干细胞(MuSC)活性。肌源性调节因子,包括成肌细胞测定蛋白1(MyoD),调节MuSCs的命运转变。然而,MYOD在此过程中的直接作用目标尚不完全清楚。使用先前建立的MyoD敲入(MyoD-KI)小鼠,我们发现MyoD靶向双特异性磷酸酶(Dusp)13和Dusp27。在Dusp13:Dusp27双敲除(DKO)小鼠中,损伤后肌肉再生能力降低。此外,MyoD-KI小鼠MyoD高表达MuSCs的单细胞RNA测序显示,Dusp13和Dusp27仅在MyoD高表达MuSCs的特定群体中表达,也表达Myogenin。在MuSC中过度表达Dusp13导致过早的肌肉分化。因此,我们提出了一个模型,其中DUSP13和DUSP27有助于MuSCs在肌生成过程中从增殖到分化的命运转变。