Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

Juan Antonio Guadix, Valeria V. Orlova, Elisa Giacomelli, Milena Bellin, Marcelo C. Ribeiro, Christine L. Mummery, José M. Pérez-Pomares*, Robert Passier

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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. The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair.

Original languageEnglish
Pages (from-to)1754-1764
Number of pages11
JournalStem cell reports
Issue number6
Publication statusPublished - 12 Dec 2017


  • cardiovascular
  • differentiation
  • human pluripotent stem cells
  • proepicardium
  • progenitor cells


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