Epicardium and myocardium originate from a common cardiogenic precursor pool

During development, the epicardium, an epithelial layer that covers the heart, gives rise to a large portion of the nonmyocardial cells present in the heart. The epicardium arises from a structure, called the proepicardium, which forms at the inflow of the developing heart. By epithelial-to-mesenchymal transformation, mesenchymal cells are formed that will subsequently populate the stroma of the proepicardium and the subepicardium. Based on labeling analysis, the proepicardium and part of the myocardium have been shown to be derived from a common cardiogenic precursor population. In this review, we will discuss the common cardiogenic origin of proepicardial and myocardial cells, the underlying processes and factors that play a role in the separation of the lineages, and their potential role in cardiac regenerative approaches.