Abstract
SummaryThe epicardium is essential during cardiac development, homeostasis, and repair, and yet fundamental insights into its underlying cell biology, notably epicardium formation, lineage heterogeneity, and functional cross-talk with other cell types in the heart, are currently lacking. In this study, we investigated epicardial heterogeneity and the functional diversity of discrete epicardial subpopulations in the developing zebrafish heart. Single-cell RNA sequencing uncovered three epicardial subpopulations with specific genetic programs and distinctive spatial distribution. Perturbation of unique gene signatures uncovered specific functions associated with each subpopulation and established epicardial roles in cell adhesion, migration, and chemotaxis as a mechanism for recruitment of leukocytes into the heart. Understanding which mechanisms epicardial cells employ to establish a functional epicardium and how they communicate with other cardiovascular cell types during development will bring us closer to repairing cellular relationships that are disrupted during cardiovascular disease.
Highlights
During embryonic development, numerous cardiovascular cell types interact to build and maintain a functional heart
Expression of tcf21, tbx18, and wt1b Is Heterogeneous in the Developing Zebrafish Epicardium
Expression of Tcf21, Tbx18, and Wt1 is restricted to subsets of epicardial cells in the developing mouse and chick heart (Braitsch et al, 2012)
Summary
Numerous cardiovascular cell types interact to build and maintain a functional heart. The epicardium is a mesothelial cell sheet that covers the heart’s outer surface and, together with the myocardium and the endocardium, forms the wall of the heart 72 hpf, proepicardial cells translocate to the ventricle via pericardial fluid movements, where they form a continuous cell layer (Peralta et al, 2013). A subset of epicardial cells undergoes an epithelial-to-mesenchymal transition, giving rise to epicardium-derived cells (EPDCs) (von Gise and Pu, 2012). These delaminating cells invade the subepicardial compartment and colonize the underlying myocardium to nurture the further growth of the developing heart muscle and coronary vessels by acting as an essential source of mitogens (Pérez-Pomares and de La Pompa, 2011)
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