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单细胞 RNA 测序解析了小鼠腹主动脉瘤内免疫细胞的分布。

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

机构信息

Departments of Cardiology (Z.Y., L.S., Y.W., Z.C.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

State Key Laboratory of Transvascular Implantation Devices, China (Z.Y., L.S., Y.W., Z.C.).

出版信息

Arterioscler Thromb Vasc Biol. 2024 Sep;44(9):1986-2003. doi: 10.1161/ATVBAHA.124.321129. Epub 2024 Jul 25.

DOI:10.1161/ATVBAHA.124.321129
PMID:39051127
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.

摘要

背景

炎症是腹主动脉瘤(AAA)发展的一个关键组成部分,但对于免疫细胞及其相互作用在这一过程中的作用的了解有限。

方法

我们使用单细胞 RNA 转录组分析,在单细胞水平上对弹性蛋白酶诱导的小鼠 AAA 中的 CD45 细胞群进行了解构。我们从不同时间点的小鼠 AAA 组织中分离出每一组免疫细胞,并将其分为几个亚型,列出显著差异表达的基因,探索免疫细胞的发育轨迹,并展示它们之间的相互作用。

结果

我们的研究结果显示,与正常主动脉相比,AAA 微环境中的几种免疫细胞亚群(包括巨噬细胞、树突状细胞和 T 细胞)存在显著差异。特别是,传统树突状细胞 1 型仅存在于 AAA 组织中,而不存在于正常主动脉中。通过 CellChat 分析,我们鉴定了几种细胞间通讯途径,如 visfatin,它靶向单核细胞分化和中性粒细胞与树突状细胞之间的中性粒细胞细胞外陷阱介导的相互作用,这可能有助于 AAA 的发展。其中一些途径在人类 AAA 中得到了验证。

结论

尽管没有外部致病刺激,AAA 组织仍会发展出涉及多种免疫细胞的复杂炎症微环境。深入研究炎症网络将为 AAA 患者提供新的治疗策略。

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