Multi-omics data reveal the origin of cardiac myxoma
Cardiac myxoma, the most common primary heart tumor, remains poorly understood at the molecular level. Here, we combined single-nucleus RNA sequencing, third-generation transcriptomics, and untargeted metabolomics to dissect its origin and pathology. Single-cell analyses demonstrate an endothelial origin driven by aberrant endothelial-to-mesenchymal transition (EndMT), with pseudotime and RNA-velocity tracing a continuum from endothelial-like to mesenchymal-like and metabolically active states. We identify two distinct myxoma subtypes: Subtype 1, marked by MAPK/WNT/EGFR pathway activation, and Subtype 2, characterized by ribosomal and oxidative phosphorylation signatures alongside immune-evasive programs. Third-generation data highlight extracellular matrix remodeling and endothelial signaling, while metabolomics reveal dysregulated purine, nicotinic acid, and nicotinamide metabolism. Notably, MET-PTK2 signaling emerges as a potential driver of tumor initiation and progression. These integrated findings define the cellular architecture and metabolic adaptations of cardiac myxoma and lay the foundation for future interventions.
Authors
- Chengming Fan (ORCID: https://orcid.org/0000-0002-1352-8301)
- Longke Ran (ORCID: https://orcid.org/0000-0002-6434-5521)
- Jie Lan (ORCID: https://orcid.org/0000-0002-4962-8363)
- Xiushan Wu (ORCID: https://orcid.org/0000-0001-8431-4266)
- Mingzhu Yin (ORCID: https://orcid.org/0000-0002-6964-7131)
- Huajun Sun (ORCID: https://orcid.org/0000-0001-9035-2824)
- Chenqing Zheng (ORCID: https://orcid.org/0000-0002-4566-7947)
- Xiaoping Li (ORCID: https://orcid.org/0000-0001-5580-5605)
- Shengzhong Frank Liu (ORCID: https://orcid.org/0000-0002-6338-852X)
- Keli Huang (ORCID: https://orcid.org/0000-0002-7364-6916)
- Wanfeng Zhang (ORCID: https://orcid.org/0000-0002-8717-1552)
- Rensheng Lai
Institutions
- Central South University (CN)
- University of Electronic Science and Technology of China (CN)
- Hunan Normal University (CN)
- Key Laboratory of Guangdong Province (CN)
- ShenZhen People’s Hospital (CN)
- Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN)
- Chongqing Three Gorges Central Hospital (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Second Xiangya Hospital of Central South University (CN)
- Chongqing Cancer Hospital (CN)
- Chongqing Three Gorges University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1038/s42003-025-08752-y
- Primary Topic
- Cardiac tumors and thrombi
- Type
- article
- Field-Weighted Citation Impact
- 0.00