Human Monocyte Heterogeneity as Revealed by High-Dimensional Mass Cytometry
Human Monocyte Heterogeneity as Revealed by High-Dimensional Mass Cytometry
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DOI：
10.1161/atvbaha.118.311022
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发表时间：
2019-01-01
影响因子：
8.7
通讯作者：
Hedrick, Catherine C.
中科院分区：
文献类型：
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作者：
Hamers, Anouk A. J.;Dinh, Huy Q.;Hedrick, Catherine C.
根据CD 14和CD 16的表面标志物表达，已经鉴定了三种不同的人单核细胞亚群。我们假设，单核细胞可能更异质的composition.Approach和结果，我们使用了高维度的质量流式细胞术与FlowSOM聚类算法，以准确地识别和定义单核细胞亚群在血液中的健康人受试者和那些与冠状动脉疾病（CAD）。为了研究新定义的单核细胞亚群的行为和功能，我们进行了RNA测序、transwell迁移和单核细胞增多试验。在这里，我们确定了8个人类单核细胞亚群的基础上，他们的表面标志物表型。我们发现这些亚群中有3个属于CD 16（+）非经典单核细胞群，4个属于CD 14（+）经典单核细胞群，说明人类单核细胞具有显著的异质性。由于非经典单核细胞在调节小鼠动脉粥样硬化中很重要，我们研究了我们新鉴定的3种非经典单核细胞在CAD受试者中的功能。我们发现在CAD受试者中Slan+ CXCR 6+非经典单核细胞亚群显著扩增，这与CAD严重程度呈正相关。这个非经典的子集可以向CXCL 16迁移，并显示出增加的红细胞能力，表明它可能发挥动脉粥样硬化的保护作用。结论-我们的数据表明，人类非经典单核细胞是一个异质性的人口，存在的几个子集的功能差异。这些子集在严重CAD的情况下改变了频率。了解这些新发现的亚群如何调节CAD对于靶向髓系细胞的基于CAD的治疗将是重要的。
Objective-Three distinct human monocyte subsets have been identified based on the surface marker expression of CD14 and CD16. We hypothesized that monocytes were likely more heterogeneous in composition.Approach and Results-We used the high dimensionality of mass cytometry together with the FlowSOM clustering algorithm to accurately identify and define monocyte subsets in blood of healthy human subjects and those with coronary artery disease (CAD). To study the behavior and functionality of the newly defined monocyte subsets, we performed RNA sequencing, transwell migration, and efferocytosis assays. Here, we identify 8 human monocyte subsets based on their surface marker phenotype. We found that 3 of these subsets fall within the CD16(+) nonclassical monocyte population and 4 subsets belong to the CD14(+) classical monocytes, illustrating significant monocyte heterogeneity in humans. As nonclassical monocytes are important in modulating atherosclerosis in mice, we studied the functions of our 3 newly identified nonclassical monocytes in subjects with CAD. We found a marked expansion of a Slan+ CXCR6+ nonclassical monocyte subset in CAD subjects, which was positively correlated with CAD severity. This nonclassical subset can migrate towards CXCL16 and shows an increased efferocytosis capacity, indicating it may play an atheroprotective role.Conclusions-Our data demonstrate that human nonclassical monocytes are a heterogeneous population, existing of several subsets with functional differences. These subsets have changed frequencies in the setting of severe CAD. Understanding how these newly identified subsets modulate CAD will be important for CAD-based therapies that target myeloid cells.