Single-cell analysis of human fetal epicardium reveals its cellular composition and identifies CRIP1 as a modulator of EMT.

The epicardium plays an essential role in cardiogenesis by providing cardiac cell types and paracrine cues to the developing myocardium. The human adult epicardium is quiescent, but recapitulation of developmental features may contribute to adult cardiac repair. The cell fate of epicardial cells is proposed to be determined by the developmental persistence of specific subpopulations. Reports on this epicardial heterogeneity have been inconsistent, and data regarding the human developing epicardium are scarce. Here we specifically isolated human fetal epicardium and used single-cell RNA sequencing to define its composition and to identify regulators of developmental processes. Few specific subpopulations were observed, but a clear distinction between epithelial and mesenchymal cells was present, resulting in novel population-specific markers. Additionally, we identified CRIP1 as a previously unknown regulator involved in epicardial epithelial-to-mesenchymal transition. Overall, our human fetal epicardial cell-enriched dataset provides an excellent platform to study the developing epicardium in great detail.

Epicardial Contribution to the Developing and Injured Heart: Exploring the Cellular Composition of the Epicardium.

The epicardium is an essential cell population during cardiac development. It contributes different cell types to the developing heart through epithelial-to-mesenchymal transition (EMT) and it secretes paracrine factors that support cardiac tissue formation. In the adult heart the epicardium is a quiescent layer of cells which can be reactivated upon ischemic injury, initiating an embryonic-like response in the epicardium that contributes to post-injury repair processes. Therefore, the epicardial layer is considered an interesting target population to stimulate endogenous repair mechanisms. To date it is still not clear whether there are distinct cell populations in the epicardium that contribute to specific lineages or aid in cardiac repair, or that the epicardium functions as a whole. To address this putative heterogeneity, novel techniques such as single cell RNA sequencing (scRNA seq) are being applied. In this review, we summarize the role of the epicardium during development and after injury and provide an overview of the most recent insights into the cellular composition and diversity of the epicardium.