Revealing the crucial roles of suppressive immune microenvironment in cardiac myxoma progression.

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Signal Transduction and Targeted Therapy Pub Date : 2024-08-02 DOI:10.1038/s41392-024-01912-2
Zedong Jiang, Qianlong Kang, Hong Qian, Zhijie Xu, Huan Tong, Jiaqing Yang, Li Li, Renwei Li, Guangqi Li, Fei Chen, Nan Lin, Yunuo Zhao, Huashan Shi, Juan Huang, Xuelei Ma
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Abstract

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.

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揭示抑制性免疫微环境在心肌瘤进展中的关键作用。
心脏肌瘤是一种常见的心脏肿瘤,有可能危及生命。然而,人们对这种疾病的细胞组成仍不甚了解。为了填补这一空白,我们通过单细胞测序分析了心脏肌瘤组织中的 75,641 个细胞。我们确定了心肌肌瘤细胞群,它们与成纤维细胞相似,但因磷酸二酯酶以及与细胞增殖、分化和粘附相关的基因表达增多而与成纤维细胞区分开来。细胞群的临床相关性表明,肌瘤细胞和 M2 样巨噬细胞浸润的比例较高,而且它们的空间相互作用增强,这些都是导致栓塞发生的重要原因。肌瘤周围的免疫细胞表现出抑制性特征,T 细胞的功能受损,表现为 GZMK 和 TOX 的表达,以及大量表达生长因子(如 PDGFC)的促瘤巨噬细胞的浸润。此外,体外共培养实验表明,巨噬细胞能显著促进肌瘤细胞的生长。总之,本研究提出了一个全面的心脏肌瘤单细胞图谱,强调了肌瘤细胞的异质性及其对免疫细胞的协同影响。这些发现揭示了心肌肌瘤复杂的病理生物学,并提出了潜在的干预目标。
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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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