A Notch/COLV/CALCR signalling cascade actively maintains muscle stem cell quiescence. satellite cells are in direct contact with the plasma membrane of the myofibre (black outline) and an overlying basement membrane (blue line). Activation of the Notch receptor is achieved by ligand (likely Dll-1 or Dll4) present on the muscle fibre. Induction of Col5a1 and Col5a3 (and also Col6a1/2) genes occurs via distal regulatory elements (blue box). Satellite cell-produced COLV is deposited under the basement membrane and acts as a surrogate ligand of the plasma membrane receptor CALCR, expressed also by the satellite cells, thereby propagating a cell-autonomous signalling system in the local niche. In the absence of COLV (deletion of Col5a1) the quiescent niche is disturbed, CALCR signalling is abrogated, and satellite cells spontaneously differentiate and fuse to myofibres, leading to exhaustion of the muscle stem cell pool.