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

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Abstract

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
Volume9
Issue number6
DOIs
Publication statusPublished - 12 Dec 2017

Fingerprint

Pluripotent Stem Cells
Stem cells
Cell Differentiation
Stem Cells
Bone Morphogenetic Protein 4
Tretinoin
Induced Pluripotent Stem Cells
Genes
Human Development
Chick Embryo
Cell- and Tissue-Based Therapy
Coculture Techniques
Transcription
Regeneration
Myocardium
Cell culture
Down-Regulation
Assays
Repair
Adhesion

Keywords

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

Cite this

Guadix, Juan Antonio ; Orlova, Valeria V. ; Giacomelli, Elisa ; Bellin, Milena ; Ribeiro, Marcelo C. ; Mummery, Christine L. ; Pérez-Pomares, José M. ; Passier, Robert. / Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells. In: Stem cell reports. 2017 ; Vol. 9, No. 6. pp. 1754-1764.
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Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells. / Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert.

In: Stem cell reports, Vol. 9, No. 6, 12.12.2017, p. 1754-1764.

Research output: Contribution to journalArticleAcademicpeer-review

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