#IDIBELLseminars: Embryonic origin of cardiac fibroblasts: on and off the record

The epicardium is the outermost tissue layer of the heart. The epicardium forms from the proepicardium (PE), i.e. the transient extracardiac structure that contains epicardial progenitors. The (pro)epicardial cell lineage, via cell- and non-cell-autonomous mechanisms, is crucial for proper cardiac formation. Most importantly, the embryonic epicardium seeds the heart with fibroblast cells that will play key roles in the pathologic response of the adult heart to adverse and pathologic conditions. However, our knowledge on the molecular and cellular mechanisms regulating epicardial progenitor cell conversion into primitive epicardial cells, and then to mesenchymal epicardial-derived cells (EPDCs), is very limited. In this talk we will provide new data on the embryonic formation of these cell progenitor cells as well as on the relation these events have with reparative responses in the diseased heart.

Hosted by Angel Raya – Stem cell potency

Prof. J.M. Pérez-Pomares (b. 1972) got his PhD on Cardiovascular Developmental Biology from the University of Málaga (UMA) in 2000. After short scientific visits to the USA and Germany, and a two-year post-doctoral period at the Department of Cell Biology and Anatomy, Medical University of South Carolina (Charleston, SC, USA, 2000-2002), he returned to Spain to work as Research Assistant (2002-2004), Assistant Professor (2004-2010), and Associate Professor (2010-2018). In 2018 he was promoted to Full Professor and he is the current Chair of the Department of Animal Biology, UMA (2020-2024). Prof. Pérez-Pomares is the PI of the “Cardiovascular Development and Disease” (DeCA) team at UMA, Group Leader at Málaga’s Institute of Biomedicine IBIMA, and Visiting Scientist at the National Center for Cardiovascular Research (CNIC, Madrid).
Prof. Pérez-Pomares’ research has focused in the study of epicardial embryonic development and its impact in heart morphogenesis and adult cardiac disease. Dr. Pérez-Pomares’ work demonstrated, for the first time, that the epicardium is able to initiate an epithelial-to- mesenchymal transition (EMT) that results in the appearance of a novel population of mesenchymal cells displaying a high morphogenetic potential. EPDCs were shown to differentiate into multiple mesodermal cell types, including coronary endothelial and smooth muscle cells, and fibroblasts, among other cell kinds (Pérez-Pomares et al., 1998, PMID: 9337131; 2002, PMID: 12086469). This work was also crucial to decipher the non-cell autonomous, epicardial-mediated role played by retinoic acid in ventricular myocardial growth (Guadix et al., 2011, PMID: 21343363). All these findings led to the hypothesis, that EPDC could be a cardiac cell progenitor type, and even a cellular substrate to repair the damaged heart (Wessels & Pérez-Pomares, 2004, PMID: 14699633). The analysis of EPDC contribution to the coronary vascular system resulted in a series of important publications that have set a standard in the field (Cano et al., 2016; Pérez-Pomares et al., 2016). Today, the analysis of epicardial-derived cardiac fibroblasts and their role in cardiac fibrosis is a main research line in the DeCA laboratory.