Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells.

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)...

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Detalles Bibliográficos
Autores: Guadix, Juan Antonio, Orlova, Valeria V, Giacomelli, Elisa, Bellin, Milena, Ribeiro, Marcelo C, Mummery, Christine L, Pérez-Pomares, José M, Passier, Robert
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17347
Acceso en línea:http://hdl.handle.net/20.500.12105/17347
Access Level:acceso abierto
Palabra clave:cardiovascular
differentiation
human pluripotent stem cells
proepicardium
progenitor cells
Animals
Bone Morphogenetic Protein 4
Cardiovascular System
Cell Adhesion
Cell Culture Techniques
Cell Differentiation
Chick Embryo
Embryonic Development
Gene Expression Regulation, Developmental
Heart
Humans
Induced Pluripotent Stem Cells
Myocardium
Myocytes, Cardiac
Pericardium
Receptor, Platelet-Derived Growth Factor alpha
Stem Cells
Tretinoin
Descripción
Sumario: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.

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