Graduate Student Sungkyunkwan University School of Medicine Suwon, Kyonggi-do, Republic of Korea
Abstract: The early development of the heart involves the formation of a heart tube that undergoes elongation and looping, processes critical for shaping the mature heart. Disruptions in these morphogenetic events lead to congenital heart diseases, which affect 1% of newborns. Despite significant progress, our understanding of human heart development and the etiology of congenital malformations remains limited, largely due to the reliance on animal models and the absence of human in vitro systems capable of replicating these dynamic processes. Existing human heart organoids fail to capture the elongation and looping of the heart tube. Through enhancing self-organization with minimal external cardiogenic signaling cues, we generated elongating heart organoids (eHOs) that successfully undergo heart tube formation, elongation, and looping, mimicking key aspects of natural heart morphogenesis. These eHOs displayed distinct regions corresponding to the atrium, ventricle, and sinus venosus along the longitudinal axis of the heart tube. Additionally, the eHOs exhibited directional propagation of contractile waves initiated from the sinus venosus region, mirroring the functional integration of the cardiac domains. Remarkably, the eHOs also generated proepicardial cells, which protruded from the sinus venosus and migrated away to form an epicardial layer. This novel platform offers an unprecedented human in vitro model of early heart development, enabling mechanistic studies of heart tube morphogenesis and providing new opportunities for investigating the origins of congenital heart defects. Furthermore, these eHOs hold promise for advancing preventive and therapeutic strategies targeting congenital heart diseases.
