Interplay of cell–cell contacts and RhoA/MRTF‐A signaling regulates cardiomyocyte identity
Dorn et al
Cell–cell and cell–matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell–cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA‐ROCKsignaling to maintain an activeMRTF/SRFtranscriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis‐inducing signals. We also demonstrate byin vivofate mapping and clonal analysis of cardiac progenitors that cardiac fat and a subset of cardiac muscle arise from a common precursor expressing Isl1 and Wt1 during heart development, suggesting related mechanisms of determination between the two lineages.
