Single-cell RNA-Seq reveals CVI-mAb-induced Lyve1+M2-like macrophages reduce atherosclerotic plaque area in Apoe-/- mice
Single-cell RNA-Seq reveals CVI-mAb-induced Lyve1+M2-like macrophages reduce atherosclerotic plaque area in Apoe-/- mice
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DOI：
10.1016/j.intimp.2023.109794
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发表时间：
2023-02-01
影响因子：
5.6
通讯作者：
Zhao, Ming
中科院分区：
文献类型：
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作者：
Duan, Rui;Liu, Yan;Zhao, Ming
背景：动脉粥样硬化是一种由脂质失衡引起的自身免疫性疾病。巨噬细胞参与动脉粥样硬化的发生发展。虽然许多研究已经利用单细胞RNA测序来确定各种巨噬细胞表型在动脉粥样硬化中的作用，但对治疗动脉粥样硬化有好处的巨噬细胞亚群还没有完全了解。方法：对正常饮食(ND)、高脂饮食(HFD)和高脂饮食(HFD)加VI型胶原单抗(CVI-mAb)处理的载脂蛋白E缺陷(APOE-/-)小鼠的F4/80+巨噬细胞进行单细胞RNA测序分析。与其他组相比，在接受CVI-mAb治疗的HFD患者中，几乎只能在APOE-/-小鼠身上检测到表达透明质酸受体LYVE1的M2样巨噬细胞。差异基因表达和基因本体论分析揭示了区分这一巨噬细胞亚群的特定基因表达模式，并揭示了其功能。结果：LYVE1+M2巨噬细胞在脂质代谢中具有特殊功能。LYVE1+M2样巨噬细胞经荧光激活细胞分选(FACS)分选后过继转移至饲喂HFD的APOE-/-小鼠。结论：LYVE1+M2巨噬细胞可减少APOE-/-小鼠的斑块面积。
Background: Atherosclerosis is a lipid imbalance-induced autoimmune disease. Macrophages participate in the development and progression of atherosclerosis. Although numerous studies have utilized single-cell RNA sequencing to identify the role of various macrophage phenotypes in atherosclerosis, the macrophage sub-populations that have therapeutic benefits against atherosclerosis are not fully understood. Methods: In this study, a single-cell RNA sequencing analysis was performed on the F4/80+ macrophages of apolipoprotein E-deficient (Apoe-/-) mice on a normal diet (ND), a high-fat diet (HFD), and a high-fat diet (HFD) with collagen VI monoclonal antibodies (CVI-mAb) treatment. A population of M2-like macrophages expressing the hyaluronan receptor Lyve1 was almost exclusively detectable in Apoe-/-mice on an HFD with CVI-mAb treatment, compared with other groups. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns that distinguished this macrophage subset and uncovered its functions. Results: Lyve1+ M2 macrophages appear to have specialized functions in lipid metabolism. Lyve1+ M2-like macrophages were sorted via fluorescence-activated cell sorting (FACS) and adoptively transferred to Apoe-/-mice fed an HFD. Conclusion: Our result showed that Lyve1+ M2 macrophages could reduce the plaque areas in Apoe-/-mice.