Aims Accumulation of mononuclear phagocytes (monocytes, macrophages and dendritic cells) in the vessel wall is a hallmark of atherosclerosis. Using integrated single-cell analysis of mouse and human atherosclerosis, we here aimed to refine the nomenclature of mononuclear phagocytes in atherosclerotic vessels, and to compare their transcriptomic profiles in mouse and human disease. Methods and results We integrated 12 scRNA-seq datasets of immune cells isolated from healthy or atherosclerotic mouse aortas, and data from 11 patients (n = 4 coronary vessels, n = 7 carotid endarterectomy specimens) from two studies. Integration of mouse data identified subpopulations with discrete transcriptomic signatures within previously described populations of aortic resident (Lyve1), inflammatory (Il1b), as well as foamy (Trem2hi) macrophages. We identified unique transcriptomic features distinguishing aortic intimal resident macrophages from atherosclerosis-associated Trem2hi macrophages. Also, populations of Xcr1+ type 1 classical dendritic cells (cDC1), Cd209a+ cDC2 and mature DCs (Ccr7, Fscn1) with a ‘mregDC’ signature were detected. In humans, we uncovered macrophage and dendritic cell populations with gene expression patterns similar to those observed in mice. In particular, core transcripts of the foamy/Trem2hi signature (TREM2, SPP1, GPNMB, CD9) mapped to a specific population of macrophages in human lesions. Comparison of mouse and human data and direct cross-species data integration suggested transcriptionally similar macrophage and dendritic cell populations in mice and humans. Conclusions We refined the nomenclature of mononuclear phagocytes in mouse atherosclerotic vessels, and show conserved transcriptomics features of macrophages and dendritic cells in atherosclerosis in mice and humans, emphasizing the relevance of mouse models to study mononuclear phagocytes in atherosclerosis.

中文翻译：

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基于集成单细胞分析的小鼠和人动脉粥样硬化血管单核吞噬细胞分类


目的 血管壁中单核吞噬细胞（单核细胞、巨噬细胞和树突状细胞）的积累是动脉粥样硬化的标志。利用小鼠和人类动脉粥样硬化的综合单细胞分析，我们的目的是完善动脉粥样硬化血管中单核吞噬细胞的命名法，并比较它们在小鼠和人类疾病中的转录组谱。方法和结果 我们整合了从健康或动脉粥样硬化小鼠主动脉中分离出的免疫细胞的 12 个 scRNA-seq 数据集，以及来自两项研究的 11 名患者（n = 4 条冠状血管，n = 7 条颈动脉内膜切除标本）的数据。小鼠数据的整合确定了先前描述的主动脉驻留（Lyve1）、炎症（Il1b）以及泡沫（Trem2hi）巨噬细胞群体中具有离散转录组特征的亚群。我们发现了独特的转录组特征，将主动脉内膜驻留巨噬细胞与动脉粥样硬化相关的 Trem2hi 巨噬细胞区分开来。此外，还检测到 Xcr1+ 1 型经典树突细胞 (cDC1)、Cd209a+ cDC2 和具有“mregDC”特征的成熟 DC（Ccr7、Fscn1）群体。在人类中，我们发现巨噬细胞和树突状细胞群的基因表达模式与在小鼠中观察到的相似。特别是，foamy/Trem2hi 特征（TREM2、SPP1、GPNMB、CD9）的核心转录物映射到人类病变中特定的巨噬细胞群。小鼠和人类数据的比较以及直接跨物种数据整合表明小鼠和人类的巨噬细胞和树突细胞群在转录上相似。 结论 我们改进了小鼠动脉粥样硬化血管中单核吞噬细胞的命名法，并显示了小鼠和人类动脉粥样硬化中巨噬细胞和树突状细胞的保守转录组学特征，强调了小鼠模型与研究动脉粥样硬化中单核吞噬细胞的相关性。