RT Journal Article T1 Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells. A1 Guadix, Juan Antonio A1 Orlova, Valeria V A1 Giacomelli, Elisa A1 Bellin, Milena A1 Ribeiro, Marcelo C A1 Mummery, Christine L A1 Pérez-Pomares, José M A1 Passier, Robert K1 cardiovascular K1 differentiation K1 human pluripotent stem cells K1 proepicardium K1 progenitor cells AB Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA) and bone morphogenetic protein 4 (BMP4) promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (pro)epicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (pro)epicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (pro)epicardial-like cells displaying functional properties (adhesion and spreading over the myocardium) of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (pro)epicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. YR 2017 FD 2017-11-22 LK http://hdl.handle.net/10668/11845 UL http://hdl.handle.net/10668/11845 LA en DS RISalud RD Apr 7, 2025