King's College London London, England, United Kingdom
Abstract: Organoids can recapitulate many aspects of the complex structures and functions corresponding to in vivo tissue. This makes them powerful models for studying development, physiology, and disease. Current cardiac organoid models lack the paracrine signalling from surrounding tissues as well as vascular networks with a perfusable tube formation. In this current study, we generate human multilineage cardiac organoids by first forming gastruloids which mimic key features of early embryonic development and then inducing cardiovascular differentiation. Single-cell RNA-seq analysis and immunostaining revealed that the cardiac organoids generate multiple cell types alongside cells from cardiovascular lineages such as haematopoietic progenitors and endodermal cells. Immunofluorescence staining revealed the cardiac organoids contained a network of vascular endothelial cells with cardiomyocytes found encapsulated in a layer of epicardial cells. Transcriptomic analysis of cardiac organoids taken at different timepoints during differentiation reveal how these organoids closely mimic early in vivo cardiac development with early upregulation of genes associated with the primitive streak, and then development into cardiac progenitors. Moreover, upregulation of genes associated with the yolk sac and primitive haematopoiesis after cardiac induction were observed and found that potential haematopoietic progenitors and erythroid-like cells are enclosed in a vascular structure of endothelial cells within a yolk sac-like cyst. These results suggest that our organoid model could be an excellent model to recapitulate early cardiac and haematopoietic development.
