Cardiac Cell Plasticity and Its Role in Heart Repair

A novel and emerging ares of investigation in our laboratory is to understand the role of cardiac cell plasticity in heart repair. Cardiac fibroblasts were thought to be terminally differentiated cells incapable of adopting alternative cell fates. In a recent papoer (Nature 2014, 514; 585-590), we have challenged this dogma and demonstrated that exhibit considerable degree of plasticity in the injured heart. Injury via a p53 mediated mechanism enables fibroblasts to adopt alternative cell fates such as endothelial cell fates. We termed this new biological phenomenon as mesenchymal-endothelial-transition (MEndoT) and showed that augmentation of MEndoT led to greater neovascularization after cardiac injury and augmented cardiac repair. We are actively invedstigating such mechanisms of cell plasticity after cardiac injury and how such mechanisms can be modulated for therapeutic benefit.

 

Another highly plastic cardiac cell is the epicardium. The epicardium is a single layer of epithelial cells, that surrounds the heart. Although the epicardium is critically important for cardiac development (gives rise to smooth muscle cells, fibroblasts and pericytes), little is known about the function of the epicardium in the adult heart. We have recently demonstrated that the epicardium undergoes epithelial-mesenchymal-transition in a Wnt dependent manner after cardiac injury and generates cardiac fibroblasts that reside in the subepicardial space and contribute to cardiac fibrosis.  The molecular regulation of epicardial EMT, identification of precursors in the epicardium that give rise to cardiac fibroblasts and its role in wound healing form another major focus in our laboratory.