Single-cell transcriptional analysis of developmental maturation strategies for human pluripotent stem cell-derived heart organoids

Human pluripotent stem cells possess the ability to recapitulate key events of mammalian organogenesis in vitro, including heart development. Previously-described human heart organoid protocols elicit early embryonic-like cardiac phenotypes and morphologies. We hypothesized that human heart organoids can be made significantly more complex and physiologically relevant through the implementation of in utero gestational biochemical phenomena. Here, we designed and applied multiple developmental maturation strategies on our human heart organoids for a period of 10 days. Our data reveals the emergence of atrial and ventricular cardiomyocyte populations, valvular cells, epicardial cells, proepicardial-derived cells, endothelial cells, stromal cells, conductance cells, and cardiac progenitors, all of them cell types present in the primitive heart tube. Overall design: Single-cell RNA-sequencing of various developmentally maturated human heart organoids