McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada.
McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada; Division of Cardiac Surgery, Department of Surgery, University of Toronto, Toronto, ON M5G1L7, Canada.
Cell Stem Cell. 2021 Jan 7;28(1):96-111.e7. doi: 10.1016/j.stem.2020.10.003. Epub 2020 Nov 2.
The embryonic endocardium is essential for early heart development as it functions to induce trabecular myocardium, the first heart tissue to form, and is the source of the cells that make up the valves and a portion of the coronary vasculature. With this potential, human endocardial cells could provide unique therapeutic opportunities that include engineering biological valves and cell-based therapy strategies to replace coronary vasculature in damaged hearts. To access human endocardial cells, we generated a human pluripotent stem cell (hPSC)-derived endothelial population that displays many characteristics of endocardium, including expression of the cohort of genes that identifies this lineage in vivo, the capacity to induce a trabecular fate in immature cardiomyocytes in vitro, and the ability to undergo an endothelial-to-mesenchymal transition. Analyses of the signaling pathways required for development of the hPSC-derived endocardial cells identified a novel role for BMP10 in the specification of this lineage from cardiovascular mesoderm.
胚胎心内膜对于早期心脏发育至关重要，因为它可以诱导小梁心肌的形成，而小梁心肌是最早形成的心脏组织，并且是瓣膜和部分冠状血管的细胞来源。基于这一潜力，人类心内膜细胞可能提供独特的治疗机会，包括工程生物瓣膜和基于细胞的治疗策略，以替代受损心脏中的冠状血管。为了获得人类心内膜细胞，我们生成了一种人多能干细胞（hPSC）衍生的内皮细胞群体，该群体表现出许多心内膜的特征，包括表达在体内鉴定这一谱系的基因簇、在体外诱导未成熟心肌细胞形成小梁命运的能力，以及进行内皮-间充质转化的能力。对 hPSC 衍生的心内膜细胞发育所需的信号通路的分析，确定了 BMP10 在心血管中胚层特化这一谱系中的新作用。
