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

• 成果类型: Article
• 署名作者: Abilez, Oscar J.; Yang, Huaxiao; Guan, Yuan; Shen, Mengcheng; Yildirim, Zehra; Yan, Zhuge; Venkateshappa, Ravichandra; Zhao, Shane R.; Gomez, Angello H.; El-Mokahal, Marcel; Dunkenberger, Logan; Ono, Yoshikazu; Shibata, Masafumi; Nwokoye, Peter N.; Tian, Lei; Wilson, Kitchener D.; Lyall, Evan H.; Jia, Fangjun; Wo, Hung Ta; Zhou, Gao; Aldana, Bryan; Karakikes, Ioannis; Obal, Detlef; Peltz, Gary; Zarins, Christopher K.; Wu, Joseph C.
• 署名单位: Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; University of North Texas System; University of North Texas Denton; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12374
• DOI: 10.1126/science.adu9375
• 发表日期: 2025-06-05
• 关键词: pluripotent stem-cells; self-organization; cardiomyocyte differentiation; endothelial-cells; in-vitro; muscle; generation; maturation; pregnancy; expansion

摘要

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.