Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-06-05 DOI:10.1126/science.adu9375

Oscar J. Abilez, Huaxiao Yang, Yuan Guan, Mengcheng Shen, Zehra Yildirim, Yan Zhuge, Ravichandra Venkateshappa, Shane R. Zhao, Angello H. Gomez, Marcel El-Mokahal, Logan Dunkenberger, Yoshikazu Ono, Masafumi Shibata, Peter N. Nwokoye, Lei Tian, Kitchener D. Wilson, Evan H. Lyall, Fangjun Jia, Hung Ta Wo, Gao Zhou, Bryan Aldana, Ioannis Karakikes, Detlef Obal, Gary Peltz, Christopher K. Zarins, Joseph C. Wu

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Abstract

Although model organisms have provided insight into the earliest stages of cardiac and hepatic vascularization, we know very little about this process in humans because of ethical restrictions and the technical difficulty of obtaining embryos during very early development. In this study, we demonstrate that micropatterned human pluripotent stem cell–derived gastruloids enable in vitro modeling of the earliest stages of vascularization. We identify a combination of vascular-inducing factors that give rise to cardiac vascularized organoids with a spatially organized and branched vascular network. To show the broader utility of our vascularization strategy, we use the same vascular-inducing factors to produce hepatic vascularized organoids. Our results suggest that a conserved developmental program generates the vasculature within different types of organs.

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类胃原体能够模拟人类心脏和肝脏血管形成的最早阶段

尽管模式生物已经为心脏和肝脏血管形成的早期阶段提供了见解，但由于伦理限制和在早期发育阶段获得胚胎的技术困难，我们对人类的这一过程知之甚少。在这项研究中，我们证明了微图型人类多能干细胞衍生的类胃原体能够在体外模拟血管化的最早阶段。我们确定了血管诱导因子的组合，这些因子产生了具有空间组织和分支血管网络的心脏血管化器官。为了显示我们的血管化策略的更广泛的效用，我们使用相同的血管诱导因子来产生肝脏血管化的类器官。我们的结果表明，在不同类型的器官中，一个保守的发育程序产生了脉管系统。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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