Guadix, Juan AntonioOrlova, Valeria VGiacomelli, ElisaBellin, MilenaRibeiro, Marcelo CMummery, Christine LPérez-Pomares, José MPassier, Robert2023-01-252023-01-252017-11-22http://hdl.handle.net/10668/11845Human 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/cardiovasculardifferentiationhuman pluripotent stem cellsproepicardiumprogenitor cellsAnimalsBone Morphogenetic Protein 4Cardiovascular SystemCell AdhesionCell Culture TechniquesCell DifferentiationChick EmbryoEmbryonic DevelopmentGene Expression Regulation, DevelopmentalHeartHumansInduced Pluripotent Stem CellsMyocardiumMyocytes, CardiacPericardiumReceptor, Platelet-Derived Growth Factor alphaStem CellsTretinoinresearch article29173898open access10.1016/j.stemcr.2017.10.0232213-6711PMC5785703http://www.cell.com/article/S2213671117304782/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785703/pdf