生物
诱导多能干细胞
细胞生物学
细胞外基质
Wnt信号通路
形态发生
类有机物
心脏发育
转录因子
人的心脏
干细胞
解剖
胚胎干细胞
信号转导
遗传学
基因
内科学
医学
作者
Pablo Hofbauer,Stefan M. Jahnel,Nóra Pápai,Magdalena Giesshammer,Alison Deyett,Clara Schmidt,Mirjam Penc,Katherina Tavernini,Nastasja Grdseloff,Christy Meledeth,Lavinia Ceci Ginistrelli,Claudia Ctortecka,Šejla Šalic,Maria Novatchkova,Sasha Mendjan
出处
期刊:Cell
[Elsevier]
日期:2021-05-20
卷期号:184 (12): 3299-3317.e22
被引量:298
标识
DOI:10.1016/j.cell.2021.04.034
摘要
Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.
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