Elucidating the mechanisms driving epicardial quiescence to reveal novel targets for cardiac regeneration

The outer layer of the heart, the epicardium, plays key roles in cardiac formation and repair, promoting cardiomyocyte proliferation and vessel growth in developing embryos and in species that regenerate their hearts. The epicardium is maximally active for only a short window during development. Thereafter, it downregulates characteristic genetic markers, ceases to proliferate and to invade the myocardium, and undergoes morphological change, depicting the onset of epicardial quiescence during the perinatal period. We will delineate the mechanisms that drive quiescence in the murine epicardium, with the aim of identifying molecular switches that could be targeted to restore embryonic activity to the adult epicardium. To assess translational relevance, we will develop a human iPSC-derived epicardioid model and demonstrate the feasibility of such a system to investigate and manipulate quiescence in vitro.

The transcriptomic changes that accompany the transition to quiescence will be profiled by integrated scRNA-seq across the developmental time course.

Image Credit: Lupu, Redpath & Smart. bioRxiv 2021.11.25.470003; doi: https://doi.org/10.1101/2021.11.25.470003