Figure 2. Bi-phasic requirements for TGFβ, myostatin, pp38, Wnt during muscle repair. Activated by muscle injury quiescent muscle stem cells enter cell cycle and differentiate into rapidly dividing intermediate progenitor cells that expand, when the levels of listed factors are low. Up-regulation of these factors (likely by many sources, including infiltrating leukocytes that clear the wound) is needed for productive differentiation of the intermediate progenitors into fusion-competent myoblasts and post-mitotic multi-nucleated myotubes. In vitro, intermediate progenitors can be expanded in high mitogen medium and upon withdrawal of mitogens they form multi-nucleated myotubes in culture.