Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions needed for the complex morphogenetic processes of native organogenesis. Here, we show that mouse embryonic stem cells (mESCs) can be coaxed to robustly undergo fundamental steps of early heart organogenesis with an in-vivo-like spatiotemporal fidelity. These axially patterned embryonic organoids (gastruloids) mimic embryonic development and support the generation of cardiovascular progenitors, including first and second heart fields. The cardiac progenitors self-organize into an anterior domain reminiscent of a cardiac crescent before forming a beating cardiac tissue near a putative primitive gut-like tube, from which it is separated by an endocardial-like layer. These findings unveil the surprising morphogenetic potential of mESCs to execute key aspects of organogenesis through the coordinated development of multiple tissues. This platform could be an excellent tool for studying heart development in unprecedented detail and throughput.

类器官是研究组织发育、生理学和疾病的强大模型。然而，当前的培养系统破坏了天然器官发生的复杂形态发生过程所需的诱导性组织-组织相互作用。在这里，我们展示了小鼠胚胎干细胞 (mESCs) 可以通过体内诱导稳健地经历早期心脏器官发生的基本步骤。- 类似时空保真度。这些轴向图案化的胚胎类器官 (gastruloids) 模拟胚胎发育并支持心血管祖细胞的产生，包括第一和第二心场。心脏祖细胞自组织进入前部区域，让人想起心脏新月体，然后在推定的原始肠样管附近形成跳动的心脏组织，并由心内膜样层将其与心内膜样层隔开。这些发现揭示了 mESC 通过多个组织的协调发育来执行器官发生关键方面的惊人形态发生潜力。该平台可以成为以前所未有的细节和吞吐量研究心脏发育的绝佳工具。