Purpose: The embryonic origin of coronary endothelium remains controversial. Whereas studies using avian embryos support a critical contribution of epicardial progenitor/epicardium-derived cells to coronary endothelium, genetic tagging experiments in mice suggest that proepicardial/epicardial cell differentiation into coronary endothelial cells is a rare event.
Methods : Using proepicardial/epicardial Cre drivers and different reporter lines (R26R-eYFP/R26R-eGFP) we have traced proepicardial/epicardial-derived cells.
Results: We have identified a significant contribution of these cells to coronary endothelium from embryonic to postnatal stages.
Genetically-tagged coronary endothelial cells express vascular markers (FACS and sqPCR) similar to those characterizing proepicardial angioblasts (ED9.5). Our spatio-temporal map shows that Wt1Cre-YFP+ and eGata4Cre-YFP cells incorporate to the coronary endothelium. Moreover, Wt1Cre-YFP+ and eGata4Cre-YFP cells display a preferential incorporation to presumptive coronary arteries and capillaries rather than to coronary veins. Such patterned distribution is especially evident on the left ventricular side.
Conclusion: Cells from a Wt1+ and an eGata4+ cell lineage incorporate to coronary endothelium along mouse embryogenesis. Although the contribution of proepicardial/epicardial cells to the mouse coronary endothelium is not as massive as in avian embryos, this study unambiguously confirms a significant contribution of these cells to coronary development and identifies a potential role for these cells in the patterning and organization of the coronary arterial vasculature.