02030nas a2200433 4500000000100000008004100001260001500042100002000057700001700077700001400094700001900108700001900127700001400146700003000160700001800190700002100208700002200229700002300251700001800274700002100292700002100313700001300334700002400347700001800371700001600389700001500405700001300420700001700433700002200450700001600472700001500488700002600503700001700529245010000546856005600646300001300702490000800715520087300723 2025 d c2025-06-051 aOscar J. Abilez1 aHuaxiao Yang1 aYuan Guan1 aMengcheng Shen1 aZehra Yildirim1 aYan Zhuge1 aRavichandra Venkateshappa1 aShane R. Zhao1 aAngello H. Gomez1 aMarcel El-Mokahal1 aLogan Dunkenberger1 aYoshikazu Ono1 aMasafumi Shibata1 aPeter N. Nwokoye1 aLei Tian1 aKitchener D. Wilson1 aEvan H. Lyall1 aFangjun Jia1 aHung Ta Wo1 aGao Zhou1 aBryan Aldana1 aIoannis Karakikes1 aDetlef Obal1 aGary Peltz1 aChristopher K. Zarins1 aJoseph C. Wu00aGastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization uhttps://www.science.org/doi/10.1126/science.adu9375 aeadu93750 v3883 aAlthough 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.