Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Department of Cardiology and Angiology I, University Heart Center Freiburg.
Curr Opin Lipidol. 2018 Oct;29(5):389-396. doi: 10.1097/MOL.0000000000000537.
The immune system plays a critical role in the development and modulation of atherosclerosis. New high-parameter technologies, including mass cytometry (CyTOF) and single-cell RNA sequencing (scRNAseq), allow for an encompassing analysis of immune cells. Unexplored marker combinations and transcriptomes can define new immune cell subsets and suggest their functions. Here, we review recent advances describing the immune cells in the artery wall of mice with and without atherosclerosis. We compare technologies and discuss limitations and advantages.
Both CyTOF and scRNAseq on leukocytes from digested aortae show 10-30 immune cell subsets. Myeloid, T, B and natural killer cells were confirmed. Although cellular functions can be inferred from RNA-Seq data, some subsets cannot be identified based on current knowledge, suggesting they may be new cell types. CyTOF and scRNAseq each identified four B-cell subsets and three macrophage subsets in the atherosclerotic aorta. Limitations include cell death caused by enzymatic digestion and the limited depth of the scRNAseq transcriptomes.
High-parameter methods are powerful tools for uncovering leukocyte diversity. CyTOF is currently more powerful at discerning leukocyte subsets in the atherosclerotic aorta, whereas scRNAseq provides more insight into their likely functions.
免疫系统在动脉粥样硬化的发生和调节中起着关键作用。新的高参数技术，包括质谱流式细胞术（CyTOF）和单细胞 RNA 测序（scRNAseq），允许对免疫细胞进行全面分析。未探索的标记组合和转录组可以定义新的免疫细胞亚群，并提示其功能。在这里，我们回顾了最近的进展，描述了有和没有动脉粥样硬化的小鼠动脉壁中的免疫细胞。我们比较了技术，并讨论了它们的局限性和优点。
从消化的主动脉中分离出的白细胞进行 CyTOF 和 scRNAseq 分析，均可显示出 10-30 种免疫细胞亚群。证实了髓样细胞、T 细胞、B 细胞和自然杀伤细胞。尽管可以从 RNA-Seq 数据推断细胞功能，但根据目前的知识，有些亚群无法识别，这表明它们可能是新的细胞类型。CyTOF 和 scRNAseq 分别在动脉粥样硬化的主动脉中鉴定出四个 B 细胞亚群和三个巨噬细胞亚群。局限性包括酶消化引起的细胞死亡和 scRNAseq 转录组的深度有限。
高参数方法是揭示白细胞多样性的有力工具。CyTOF 目前更能辨别动脉粥样硬化主动脉中的白细胞亚群，而 scRNAseq 则更能深入了解其可能的功能。
