Single-cell transcriptomics and multimodal molecular profiling revealed the oncogenesis and tumor microenvironment of cardiac myxoma.

This study investigates the distinct cellular composition of cardiac myxoma (CM), the pathways underlying its origin, and the mechanisms driving the development of diverse tumor morphologies. A comprehensive single-cell RNA sequencing (scRNA-seq) analysis was performed on five CM tissue samples and five normal atrial septum samples, encompassing the construction of a CM cell atlas, cell differentiation trajectory reconstruction, cell-cell interaction prediction, identification of cluster-specific transcription factor regulons, and assessment of tumor cell heterogeneity. Validation of scRNA-seq results was conducted through hematoxylin-eosin staining, multiplex immunofluorescence, cellular experiments, and a public database. This study profiled a total of 86,741 cells and identified 13 distinct cell sub-populations based on gene expression. Mesenchymal cells predominated in CM tissues, with high expression of calretinin. Findings from scRNA-seq analysis demonstrated that cardiac endothelial cells undergo endothelial-to-mesenchymal transition (EndoMT), giving rise to mesenchymal-like CM cells. Moreover, hematoxylin-eosin staining and multiplex immunofluorescence revealed variations in the subtypes and functions of tumor-associated fibroblasts and mural cells across different CM morphologies (lobulated and villous). This study demonstrated that CM cells exhibit mesenchymal-like characteristics and their origin is linked to the EndoMT of cardiac endothelial cells. The subtypes of tumor-associated fibroblasts and mural cells contribute to the morphological diversity of CM.