Multi-omics data reveal the origin of cardiac myxoma

Cardiac myxoma, the most common primary cardiac tumor, presents significant challenges due to its heterogeneous cellular composition and poorly defined signaling mechanisms. In this study, we applied single-nucleus RNA sequencing (snRNA-seq) to cardiac myxoma and matched normal cardiac tissues to elucidate the tumor’s cellular origin and molecular characteristics. Our analysis provides strong evidence that myxomas arise from endothelial cells. Abnormal endothelial-to-mesenchymal transition (EndMT) contributes to the coexistence of endothelial and mesenchymal phenotypes, while activation of the MET-PTK2 signaling axis appears to drive tumor progression. Pseudotime trajectory analysis revealed dynamic transitions from endothelial-mesenchymal states to metabolically active phenotypes, uncovering distinct myxoma subtypes with potential therapeutic relevance. This study highlights the value of snRNA-seq in resolving the cellular heterogeneity of rare cardiac tumors and provides a molecular framework for developing personalized therapies.