Graduate Student Sookmyung Women's University seoul, Republic of Korea
Abstract: CDON (Cell adhesion molecule-related/downregulated by oncogenes) is a key regulator in the Sonic Hedgehog (Shh) and N-cadherin signaling pathways, essential for heart development. Whole-body Cdon knockout mouse models display significant embryonic lethality, highlighting Cdon's critical role in early embryogenesis. Additionally, Cdon-deficient mouse embryonic stem cells show impaired cardiomyocyte differentiation, underscoring its importance in cardiac development. However, insights into CDON’s role in human cardiac development remain limited due to the inherent differences between human and animal models, as well as the lack of robust in vitro systems to recapitulate early heart morphogenesis. To address this gap, we generated human heart organoids from CDON-knockout induced pluripotent stem cells (iPSCs) to study its role and underlying mechanisms in human heart development. Our findings reveal that CDON deficiency leads to abnormal lateral plate mesoderm specification, leading to aberrant germ layer patterning and disrupted cardiogenesis. These defects were associated with dysregulated Wnt signaling gradients, emphasizing CDON’s crucial role in maintaining Wnt signaling balance during mesodermal and cardiac development. Furthermore, the organoids revealed structural and functional abnormalities, including reduced cardiac marker expression and disrupted organoid architecture. By leveraging human heart organoids, this study provides novel insights into the essential role of CDON in human cardiac development and offers potential therapeutic strategies to address cardiac dysfunctions resulting from CDON deficiency.
