Liu Shengzhong, Zhang Wanfeng, Sun Huajun, Zheng Chenqing, Huang Keli, Fan Chengming, Lai Rensheng, Yin Mingzhu, Lan Jie, Wu Xiushan, Ran Longke, Li Xiaoping
Department of Cardiovascular Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Bioinformatics, College of Artificial Intelligence Medicine, Chongqing Medical University, Chongqing, China.
Commun Biol. 2025 Sep 26;8(1):1373. doi: 10.1038/s42003-025-08752-y.
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.
心脏黏液瘤是最常见的原发性心脏肿瘤，在分子水平上仍未被充分了解。在这里，我们结合单核RNA测序、第三代转录组学和非靶向代谢组学来剖析其起源和病理。单细胞分析表明，其起源于内皮细胞，由异常的内皮-间充质转化（EndMT）驱动，通过拟时间和RNA速度追踪从内皮样到间充质样和代谢活跃状态的连续过程。我们识别出两种不同的黏液瘤亚型：1型，以MAPK/WNT/EGFR途径激活为特征；2型，以核糖体和氧化磷酸化特征以及免疫逃避程序为特征。第三代数据突出了细胞外基质重塑和内皮信号传导，而代谢组学揭示了嘌呤、烟酸和烟酰胺代谢失调。值得注意的是，MET-PTK2信号传导成为肿瘤发生和进展的潜在驱动因素。这些综合发现定义了心脏黏液瘤的细胞结构和代谢适应性，为未来的干预奠定了基础。
