Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

During embryonic development, the epicardium provides a source of multipotent progenitors for cardiac lineages, including pericytes, fibroblasts and coronary smooth muscle cells. The epicardium originates from a region of splanchnopleural mesoderm known as the proepicardial organ (PEO). The potential of the epicardium to contribute to coronary endothelium has been disputed, due to conflicting lineage tracing results with different PEO Cre lines. Controversy also surrounds when epicardial cell fate becomes restricted. Using single-cell RNA-sequencing, microscopy and flow cytometry-based single molecule RNA in situ hybridisation techniques, we systematically investigated the expression of five widely used epicardial markers, Wt1, Tcf21, Tbx18, Sema3d and Scx, over the course of development. We show co-expression of all markers in the PEO and epicardial layer until E13.5, then sequential downregulation as it undergoes quiescence. Markers also decrease in invading epicardium-derived progenitors, with the exception of Tcf21, lost only in epicardium-derived mural cells. Moreover, we demonstrate that the epicardium does not significantly contribute coronary endothelium. Our findings clarify a number of prevailing discrepancies in the field and support the notion that epicardial fate is not pre-determined within the PEO.

Original publication




Working paper



Publication Date