Fig. 4: Interaction between the MuSC and its microenvironment.

The MuSC attaches to the basal lamina through integrins, which preserve quiescence, though specific integrins can also promote differentiation. Cadherin proteins attach the MuSC to the fiber, which expresses Delta ligands required to maintain a Notch-ON state in the MuSC, necessary for quiescence. Notch stimulates the production of Collagen V, which binds and activates Calcitonin receptor, providing a third axis of quiescence control. Dll4 from the endothelium also sustains MuSC quiescence through Notch signaling, which in turn leads to the production of VEGFA from MuSCs. Angiopoietin-1, secreted by pericytes, further contributes to MuSC quiescence. Upon injury, GDF3 from macrophages and WISP1 from FAPs stimulate differentiation and fusion to ensure efficient regeneration.