Jiang Zedong, Kang Qianlong, Qian Hong, Xu Zhijie, Tong Huan, Yang Jiaqing, Li Li, Li Renwei, Li Guangqi, Chen Fei, Lin Nan, Zhao Yunuo, Shi Huashan, Huang Juan, Ma Xuelei
Department of Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Signal Transduct Target Ther. 2024 Aug 2;9(1):193. doi: 10.1038/s41392-024-01912-2.
Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition of this condition is still not well understood. To fill this gap, we analyzed 75,641 cells from cardiac myxoma tissues based on single-cell sequencing. We defined a population of myxoma cells, which exhibited a resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, and adhesion. The clinical relevance of the cell populations indicated a higher proportion of myxoma cells and M2-like macrophage infiltration, along with their enhanced spatial interaction, were found to significantly contribute to the occurrence of embolism. The immune cells surrounding the myxoma exhibit inhibitory characteristics, with impaired function of T cells characterized by the expression of GZMK and TOX, along with a substantial infiltration of tumor-promoting macrophages expressed growth factors such as PDGFC. Furthermore, in vitro co-culture experiments showed that macrophages promoted the growth of myxoma cells significantly. In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.
心脏黏液瘤是心脏内常见的肿瘤,有潜在的生命危险。然而,这种疾病的细胞组成仍未得到充分了解。为了填补这一空白,我们基于单细胞测序分析了来自心脏黏液瘤组织的75641个细胞。我们定义了一群黏液瘤细胞,它们与成纤维细胞相似,但通过磷酸二酯酶以及与细胞增殖、分化和黏附相关基因的表达增加而得以区分。细胞群体的临床相关性表明,黏液瘤细胞和M2样巨噬细胞浸润比例较高,以及它们增强的空间相互作用,被发现显著促成了栓塞的发生。黏液瘤周围的免疫细胞表现出抑制特征,T细胞功能受损,其特征为GZMK和TOX的表达,以及大量表达生长因子如PDGFC的促肿瘤巨噬细胞浸润。此外,体外共培养实验表明巨噬细胞显著促进了黏液瘤细胞的生长。总之,本研究展示了心脏黏液瘤全面的单细胞图谱,突出了黏液瘤细胞的异质性及其对免疫细胞的协同影响。这些发现揭示了心脏黏液瘤复杂的病理生物学机制,并提出了潜在的干预靶点。