基于单细胞转录组鉴定动脉粥样硬化自身免疫表征

Identification of autoimmune characterization of atherosclerosis based on single cell transcriptome

[目的]基于单细胞转录组生物信息学方法探讨动脉粥样硬化免疫微环境特征,挖掘免疫炎症与动脉粥样硬化之间潜在的联系。[方法]从GEO数据库中提取单细胞转录组数据集GSE159677,可视化分析颈动脉粥样硬化斑块区及其近心端毗邻非斑块区细胞组成成分,利用CellChat整合细胞间通讯网络,分析细胞间交互作用差异,识别动脉粥样硬化斑块免疫炎症信号通路差异,探索动脉粥样硬化免疫微环境中细胞间受体-配体特异性变化通路。[结果]本研究从单细胞测序的视角分析了动脉粥样硬化斑块内的细胞构成和细胞通讯。研究发现,在动脉粥样硬化斑块的细胞构成中内皮细胞和平滑肌细胞减少,而T细胞、单核细胞、巨噬细胞及软骨细胞明显增加。通过细胞通讯分析,发现树突状细胞、单核细胞、巨噬细胞、自然杀伤细胞与内皮细胞间的通讯作用及部分细胞与单核细胞间的通讯作用均有显著的改变,相关信号通路包括CXCL家族与ACRK1、CCL家族与ACRK1、MIF与CD74等配体-受体互作。MIF、ANXA1、YNF、RETN、LGASL9等对单核细胞以及NAMPT、CCL2、TNFSF12对内皮细胞的通讯改变在免疫炎症反应调控动脉粥样硬化机制中起着关键作用。[结论]免疫炎症微环境在动脉粥样硬化斑块形成过程中发挥了重要调控作用。

Aim To explore the characteristics of immune microenvironment of atherosclerosis based on the bioinformatics method of single cell transcriptome, and to explore the potential relationship between immune inflammation and atherosclerosis. Methods Single cell transcriptome data set GSE159677 was extracted from the GEO database to visually analyze the cellular components of carotid atherosclerotic plaque and its adjacent non-plaque area. CellChat was used to integrate intercellular communication networks, analyze the difference in intercellular interaction, identify the difference in the immune inflammatory signal pathway of atherosclerotic plaque, and explore the specific change pathway of intercellular receptor-ligand in the atherosclerotic immune microenvironment. Results In this study, the cellular composition, and cellular communication in atherosclerotic plaques were analyzed from the perspective of single cell sequencing. It was found that in the cellular composition of atherosclerotic plaques, endothelial cells and smooth muscle cells decreased, while T cells, monocytes, macrophages, and chondrocytes increased significantly. Through the analysis of cellular communication, it was found that there were significant changes in the communication between dendritic cells, monocytes, macrophages, natural killer cells, and endothelial cells, and between some cells and monocytes, including CXCL family and ACRK1, CCL family and ACRK1, MIF and CD74 and other ligand-receptor interactions. The communication of MIF, ANXA1, YNF, RETN, and LGASL9 to monocytes and the communication of NAMPT, CCL2, and TNFSF12 to endothelial cells play an important role in the immune inflammatory response regulating the development of atherosclerosis. Conclusion Immune inflammatory microenvironment plays an important role in the formation of atherosclerotic plaque.