A gradient of Cripto levels identifies a continuumof functional states in activated satellite cells

Skeletal muscle repair relies on satellite cells (SCs), a highly heterogenous population of adult stem cells that generate both myogenic precursors and quiescent cells. How SC heterogeneity and plasticity are regulated during muscle regeneration, remains an open question. Here we show that activated SC (ASC) pool fluctuates through a continuum of phenotypic, molecular and functional states, which are associated with a gradient of expression levels of the extracellular membrane protein Cripto. Our findings identify Cripto as a key determinant of functional heterogeneity and plasticity of the ASCs and points to Cripto downstream signaling as potential target for interventions toward enhancing SC-mediated muscle regeneration.