Embryonic organoids recapitulate early heart organogenesis

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 the fundamental steps of early heart organogenesis with an in vivo-like spatiotemporal fidelity. These axially patterned embryonic organoids support the generation of cardiovascular progenitors, as well as first and second heart field compartments. The cardiac progenitors self-organize into an anterior domain reminiscent of a cardiac crescent before forming a beating cardiac tissue near a 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.