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Multi-chamber cardioids unravel human heart development and cardiac defects
Summary
Researchers engineered a human cardioid platform that self-organizes into multi-chambered heart structures recapitulating all major embryonic compartments including left and right ventricles, atria, outflow tract, and atrioventricular canal. The platform enables direct study of genetic mutations and environmental factors including chemical exposures on human heart development in ways not possible with existing 2D or simpler 3D models.
The number one cause of human fetal death are defects in heart development. Because the human embryonic heart is inaccessible, and the impacts of mutations, drugs, and environmental factors on the specialized functions of different heart compartments are not captured by in vitro models, determining the underlying causes is difficult. Here, we established a human cardioid platform that recapitulates the development of all major embryonic heart compartments, including right and left ventricles, atria, outflow tract, and atrioventricular canal. By leveraging both 2D and 3D differentiation, we efficiently generated progenitor subsets with distinct first, anterior, and posterior second heart field identities. This advance enabled the reproducible generation of cardioids with compartment-specific in vivo-like gene expression profiles, morphologies, and functions. We used this platform to unravel the ontogeny of signal and contraction propagation between interacting heart chambers and dissect how genetic and environmental factors cause region-specific defects in the developing human heart.
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