用于模拟心腔形成和心脏毒性评估的自组装室状心脏类器官
Self-assembled chamber-like cardiac organoids for modeling cardiac chamber formation and cardiotoxicity assessment.
摘要(中文译文)
人类心脏始终是生物医学研究的核心焦点，然而在体外以结构和功能保真度捕捉早期腔室形态发生仍具挑战性。本文展示由人类多能干细胞生成类腔室心脏类器官（CCOs），其再现了心脏腔室发育的关键特征。CCO的形成由FGF、WNT、BMP、RA和AA信号的协同调控所编排，并受HAND1、TFAP2B和NR2F2等转录因子调控。这些CCO表现出稳定的自组织架构，具有心肌层、内皮层和内腔，显示自发收缩和钙瞬变。单细胞转录组学揭示了由WNT2B介导的内皮-心肌细胞相互作用，提示协调的组织模式化。我们进一步验证了RA和AA在调节腔室扩大和稳定性中的重要作用。此外，CCOs通过直接可视化药物诱导的变化，能够高效评估心脏毒性和致畸性。总之，该平台为研究心脏发育、机制研究和药理筛选提供了稳健的模型。
Abstract
The human heart remains a central focus of biomedical research, yet capturing early chamber morphogenesis in vitro with structural and functional fidelity remains challenging. Here we show the generation of chamber-like cardiac organoids (CCOs) from human pluripotent stem cells that reproduce key features of heart chamber development. CCO formation is orchestrated by coordinated FGF, WNT, BMP, RA, and AA signaling, and regulated by transcription factors including HAND1, TFAP2B and NR2F2. These CCOs exhibit stable self-organized architectures with myocardial, endothelial layers and inner chamber, displaying spontaneous contraction and calcium transients. Single-cell transcriptomics revealed endothelium-to-cardiomyocyte interactions mediated by WNT2B, suggesting coordinated tissue patterning. We further validated the essential roles of RA and AA in modulating chamber enlargement and stability. Furthermore, CCOs enable efficient evaluation of cardiotoxicity and teratogenicity through direct visualization of drug-induced changes. Together, this platform provides a robust model for studying cardiac development, mechanistic research, and pharmacological screening.
如何引用
AMA
Xinle Zou, Fanwen Wang, Huilin Zheng, Xianzhuang Liu, Tianci Kong, Rui Jiang, et al. Self-assembled chamber-like cardiac organoids for modeling cardiac chamber formation and cardiotoxicity assessment.. Nature communications. 2026; doi:10.1038/s41467-026-73822-6.
APA
Xinle Zou, Fanwen Wang, Huilin Zheng, Xianzhuang Liu, Tianci Kong, Rui Jiang, et al (2026). Self-assembled chamber-like cardiac organoids for modeling cardiac chamber formation and cardiotoxicity assessment.. Nature communications. https://doi.org/10.1038/s41467-026-73822-6
GB/T 7714
Xinle Zou, Fanwen Wang, Huilin Zheng, Xianzhuang Liu, Tianci Kong, Rui Jiang, et al. Self-assembled chamber-like cardiac organoids for modeling cardiac chamber formation and cardiotoxicity assessment.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73822-6.
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