Integrated single-cell analysis-based classification of vascular mononuclear phagocytes in mouse and human atherosclerosis.
Integrated single-cell analysis-based classification of vascular mononuclear phagocytes in mouse and human atherosclerosis.
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DOI：
10.1093/cvr/cvac161
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发表时间：
2023-07-06
影响因子：
10.8
通讯作者：
中科院分区：
文献类型：
--
作者：
单核吞噬细胞[单核细胞、巨噬细胞和树突状细胞（DC）]在血管壁中的积聚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，我们在这里的目的是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。我们整合了从健康或动脉粥样硬化小鼠动脉瘤中分离的免疫细胞的12个单细胞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。整合小鼠数据，在先前描述的主动脉驻留（Lyve1）、炎性（Il1b）以及泡沫（Trem2hi）巨噬细胞群体中鉴定出具有离散转录组特征的亚群。我们鉴定了区分主动脉内膜驻留巨噬细胞与动脉粥样硬化相关Trem2hi巨噬细胞的独特转录组学特征。此外，检测到具有"mreg-DC"特征的Xcr 1 + 1型经典DC（cDC 1）、Cd209a + cDC 2和成熟DC（Ccr 7，Fscn 1）的群体。在人类中，我们发现巨噬细胞和DC群体的基因表达模式与小鼠中观察到的相似。特别地，泡沫/Trem2hi标签的核心转录物（TREM2、SPP 1、GPNMB、CD9）映射到人类病变中的特定巨噬细胞群体。小鼠和人类数据的比较以及直接的跨物种数据整合表明小鼠和人类中的巨噬细胞和DC群体在转录上相似。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的保守转录组学特征，强调了小鼠模型研究单核吞噬细胞在动脉粥样硬化中的相关性。
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.
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DOI：
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发表时间：
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期刊：
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影响因子：
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