Institute of Experimental Biomedicine, University Hospital Würzburg, Josef Schneider Str. 2, 97080 Würzburg, Germany.
Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7, 97078 Würzburg, Germany.
Cardiovasc Res. 2023 Jul 6;119(8):1676-1689. doi: 10.1093/cvr/cvac161.
Accumulation of mononuclear phagocytes [monocytes, macrophages, and dendritic cells (DCs)] 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.
We integrated 12 single-cell RNA-sequencing (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 DCs (cDC1), Cd209a+ cDC2, and mature DCs (Ccr7, Fscn1) with a 'mreg-DC' signature were detected. In humans, we uncovered macrophage and DC 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 DC populations in mice and humans.
We refined the nomenclature of mononuclear phagocytes in mouse atherosclerotic vessels, and show conserved transcriptomic features of macrophages and DCs in atherosclerosis in mice and humans, emphasizing the relevance of mouse models to study mononuclear phagocytes in atherosclerosis.
单核吞噬细胞（单核细胞、巨噬细胞和树突状细胞[DC]）在血管壁中的积累是动脉粥样硬化的一个标志。通过对小鼠和人类动脉粥样硬化的单细胞分析的综合分析，我们旨在完善动脉粥样硬化血管中单核吞噬细胞的命名，并比较它们在小鼠和人类疾病中的转录组谱。
我们整合了 12 个从健康或动脉粥样硬化小鼠主动脉中分离的免疫细胞的单细胞 RNA 测序（scRNA-seq）数据集，以及来自两项研究的 11 名患者（n = 4 个冠状动脉血管，n = 7 个颈动脉内膜切除术标本）的数据。对小鼠数据的整合确定了以前描述的主动脉驻留（Lyve1）、炎症（Il1b）和泡沫（Trem2hi）巨噬细胞群体中具有离散转录组特征的亚群。我们确定了将主动脉内膜驻留巨噬细胞与动脉粥样硬化相关的 Trem2hi 巨噬细胞区分开来的独特转录组特征。此外，还检测到 Xcr1+ 1 型经典 DC（cDC1）、Cd209a+cDC2 和成熟 DC（Ccr7、Fscn1）的群体，具有“mreg-DC”特征。在人类中，我们发现了具有与在小鼠中观察到的基因表达模式相似的巨噬细胞和 DC 群体。特别是，泡沫/Trem2hi 特征的核心转录物（TREM2、SPP1、GPNMB、CD9）映射到人类病变中特定的巨噬细胞群体。小鼠和人类数据的比较以及直接的跨物种数据整合表明，在小鼠和人类中，巨噬细胞和 DC 群体具有转录上相似的特征。
我们完善了小鼠动脉粥样硬化血管中单核吞噬细胞的命名，并显示了小鼠和人类动脉粥样硬化中巨噬细胞和 DC 的保守转录组特征，强调了小鼠模型在研究动脉粥样硬化中单核吞噬细胞的相关性。
