Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands; Department of Animal Biology, Faculty of Sciences, University of Málaga, Instituto Malagueño de Biomedicina (IBIMA), Campus de Teatinos s/n, 29071 Málaga, Spain; BIONAND, Centro Andaluz de Nanomedicina y Biotecnología (Junta de Andalucía, Universidad de Málaga), Severo Ochoa 35, 29590 Campanillas (Málaga), Spain.
Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
Stem Cell Reports. 2017 Dec 12;9(6):1754-1764. doi: 10.1016/j.stemcr.2017.10.023. Epub 2017 Nov 22.
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.
人类多能干细胞（hPSCs）广泛用于研究心血管细胞的分化和功能。在这里，我们将 hPSC（包括胚胎和诱导的）诱导分化为原心外胚层/心外膜祖细胞，这些细胞在发育过程中覆盖心脏。添加视黄酸（RA）和骨形态发生蛋白 4（BMP4）可促进中胚层标志物 PDGFRα的表达，上调特征性（原）心外胚层祖细胞基因，并下调心肌基因的转录。我们使用体外共培养测定和将 hPSC-心外膜细胞移植到鸡胚中的体内移植来证实这些细胞的（原）心外胚层样特性。我们的数据表明，RA+BMP4 处理的 hPSC 分化为（原）心外胚层样细胞，显示出其体内对应物的功能特性（粘附和在心肌上扩散）。这些结果扩展了证据，表明 hPSC 是研究人类发育中心外胚层向心血管细胞分化以及评估其用于心脏再生的潜力的优秀模型。
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