Developmental restriction of the jaw skeletal muscle cardiogenic potential

Cardiovascular diseases are a leading cause of mortality worldwide and heart failure remains an end-stage disease with no other treatment than transplantation. A promising field to tackle heart failure is cardiomyocyte implantation. Whereas cardiomyocyte generation from pluripotent cells has shown promising results, direct derivation of cardiomyocytes from somatic stem cells is still challenging. Skeletal muscle progenitors have been extensively studied as a source of cardiac cells, due to their cellular and functional similarities. During development, the right ventricular myocardium and jaw skeletal muscles derive from a common pool of myogenic mesodermal progenitors. Previous studies have reported the derivation of cardiomyocyte-like cells specifically from adult jaw muscle stem cell populations, but not from other skeletal muscles, suggesting that developmental origin endows cardiogenic potential. Here we evaluated the cardiogenic potential of satellite cells and mesenchymal progenitor cells from the masticatory muscle by reproducing, optimizing and diversifying previously described protocols. We consistently found that stem cells from masticatory muscles are unable to differentiate into cardiac cells under any tested cardiogenic environment. Furthermore, pharmacological erasing of repressive epigenetic marks did not activate cardiogenic potential, suggesting that barriers restraining lineage plasticity are profound and unlikely to be reversed by simple exposure to cardiogenic environments.