Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.

IF 7.4 1区 医学 Q1 HEMATOLOGY
Zhen Yuan, Li Shu, Jiantao Fu, Peipei Yang, Yidong Wang, Jie Sun, Mengsha Zheng, Zhenjie Liu, Jin Yang, Jiangping Song, Shen Song, Zhejun Cai
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引用次数: 0

Abstract

Background: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited.

Methods: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them.

Results: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA.

Conclusions: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.

单细胞 RNA 测序解构了小鼠腹主动脉瘤内免疫细胞的分布。
背景:炎症是腹主动脉瘤(AAA)发病的关键因素:炎症是腹主动脉瘤(AAA)发生发展的关键因素,但人们对免疫细胞的作用及其在这一过程中的相互作用了解有限:我们利用单细胞 RNA 转录组分析,在单细胞水平上解构了弹性蛋白酶诱导的小鼠 AAA 中的 CD45+ 细胞群。我们从不同时间点的小鼠 AAA 组织中分离出各组免疫细胞,并将它们分为几种亚型,列出了显著差异表达的基因,探索了免疫细胞的发育轨迹,并证明了它们之间的相互作用:结果:我们的研究结果表明,与正常主动脉相比,AAA微环境中包括巨噬细胞、树突状细胞和T细胞在内的多个免疫细胞亚群存在明显差异。特别是传统的树突状细胞 1 型只存在于 AAA 组织中,而非正常主动脉。通过 CellChat 分析,我们发现了几种细胞间通讯途径,如针对单核细胞分化的粘蛋白和中性粒细胞胞外捕获物介导的中性粒细胞与树突状细胞之间的相互作用,这些途径可能会导致 AAA 的发生。其中一些途径在人类AAA中得到了验证:结论:尽管没有外部致病因素的刺激,AAA组织仍会形成一个复杂的炎症微环境,其中涉及大量免疫细胞。对炎症网络的深入研究将为 AAA 患者提供新的治疗策略。
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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
337
审稿时长
2-4 weeks
期刊介绍: The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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