Capturing Cardiogenesis in Gastruloids

• Published in: Cell stem cell 2021-02, Vol.28 (2), p.230-240.e6
• Main Authors: Rossi, Giuliana, Broguiere, Nicolas, Miyamoto, Matthew, Boni, Andrea, Guiet, Romain, Girgin, Mehmet, Kelly, Robert G., Kwon, Chulan, Lutolf, Matthias P.
• Format: Article
• Language: English
• Subjects: 3D cardiac tissue; Animals; cardiac organoid; cardiogenesis; development; Embryonic Development; embryonic organoids; Heart; in vitro organogenesis; Life Sciences; Mice; Mouse Embryonic Stem Cells; Organogenesis; Organoids
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2020.10.013

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. [Display omitted] •Gastruloids generate cardiovascular progenitors and form a vascular-like structure•Both first and second heart field-like progenitors are specified•Cardiac progenitors self-organize into crescent and heart tube-like beating domains•Cellular diversity and tissue-tissue interactions mimic embryonic development Rossi et al. describe an embryonic organoid model that mimics the early development of the heart, from the generation of cardiovascular precursor cells to the specification of the first and second heart fields. These axially patterned organoids support the formation of cardiac crescent and early cardiac tube-like structures while reproducing the cell diversity and tissue-tissue interactions typical of embryos.