先天性心脏病包括各种不同的结构性心脏缺陷，其中最严重的是单心室缺陷（SVD）。这些患者患有显著的发病率和死亡率；然而，我们对这些疾病的发展起因的理解是有限的。模型生物提供了一个窗口，可以观察到正常和异常的心脏发生作用，但往往无法再现患者中看到的复杂的先天性心脏缺陷。从单心室缺陷患者中获取的诱导性多能干细胞（iPSCs）的使用，为在不同的情境下研究病人衍生的心肌细胞（iPSC-CMs）中的SVD打开了大门，包括器官样体和特定室心肌细胞。由于SVD的遗传和细胞原因不清楚，患者衍生的iPSC-CMs有望揭示疾病发展机制，并作为测试疗法的平台。本文的目的是突出基于iPSC的SVD模型的最新进展。基于患者衍生的iPSC-CM 分化的最新进展，以及特定室心肌细胞和非心肌细胞类型的发展，使得在SVD发展中涉及的复杂基因和分子结构的模拟成为可能。此外，随着3D器官样体和工程心脏组织的生成，iPSC模型变得越来越复杂，为了解SVD发展的新机制提供了机会。最后，iPSC-CMs已被用于概念证明研究，证明了SVD的分子基础可能是可以为将来的治疗所针对的。尽管每个平台都有其优点和缺点，但是使用患者衍生的iPSC-CMs为病人特异性心育和SVD发展提供了窗口。干细胞模型技术在SVD模拟方面的进步有望革命我们对SVD发展起因的理解，并提供了开发和测试新治疗方法的工具。 ©2023. 作者，独家授权给Springer Science+Business Media，LLC，（Springer Nature公司的一部分）。

Congenital heart disease includes a wide variety of structural cardiac defects, the most severe of which are single ventricle defects (SVD). These patients suffer from significant morbidity and mortality; however, our understanding of the developmental etiology of these conditions is limited. Model organisms offer a window into normal and abnormal cardiogenesis yet often fail to recapitulate complex congenital heart defects seen in patients. The use of induced pluripotent stem cells (iPSCs) derived from patients with single-ventricle defects opens the door to studying SVD in patient-derived cardiomyocytes (iPSC-CMs) in a variety of different contexts, including organoids and chamber-specific cardiomyocytes. As the genetic and cellular causes of SVD are not well defined, patient-derived iPSC-CMs hold promise for uncovering mechanisms of disease development and serve as a platform for testing therapies. The purpose of this review is to highlight recent advances in iPSC-based models of SVD.Recent advances in patient-derived iPSC-CM differentiation, as well as the development of both chamber-specific and non-myocyte cardiac cell types, make it possible to model the complex genetic and molecular architecture involved in SVD development. Moreover, iPSC models have become increasingly complex with the generation of 3D organoids and engineered cardiac tissues which open the door to new mechanistic insight into SVD development. Finally, iPSC-CMs have been used in proof-of-concept studies that the molecular underpinnings of SVD may be targetable for future therapies. While each platform has its advantages and disadvantages, the use of patient-derived iPSC-CMs offers a window into patient-specific cardiogenesis and SVD development. Advancement in stem-cell based modeling of SVD promises to revolutionize our understanding of the developmental etiology of SVD and provides a tool for developing and testing new therapies.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.