Single-cell RNA-Seq reveals the transcriptional landscape and heterogeneity of skin macrophages in Vsir-/- murine psoriasis
Single-cell RNA-Seq reveals the transcriptional landscape and heterogeneity of skin macrophages in Vsir-/- murine psoriasis
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DOI：
10.7150/thno.45614
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发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Liu, Jun
中科院分区：
文献类型：
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作者：
Qie, Chenxin;Jiang, Jingwei;Liu, Jun
原理：V域免疫球蛋白T细胞激活抑制因子(VistA)是一种新的抑制性免疫检查点分子。VSIR(-/-)小鼠加重了牛皮癣样皮肤炎症。在VSIR(-/-)银屑病小鼠中，参与炎症反应的免疫细胞亚群在很大程度上是未知的。我们使用scRNA-seq作为一种无偏倚的图谱策略，在单个细胞水平上研究VsiR(-/-)银屑病小鼠皮肤中免疫细胞的异质性。方法：本研究用ImQ治疗野生型和VsiR(-/-)小鼠的右耳和剃背皮肤，连续5天诱导银屑病样皮炎。结果：从23,258个细胞中鉴定出12个主要细胞亚型。皮肤细胞以巨噬细胞、树突状细胞和成纤维细胞为主。WT组(61.29%)和VsiR(-/-)组(77.7%)免疫细胞以巨噬细胞为主。值得注意的是，在VSIR(-/-)银屑病小鼠中，树突状细胞和成纤维细胞被扩张。此外，对基因表达特征进行了评估。我们观察到Hspb1和CEBPB在VsiR(-/-)银屑病小鼠中显著上调。差异基因表达和基因本体丰富分析揭示了区分这些亚群的特定基因表达模式，并揭示了每种细胞类型的假定功能。数据分析导致在VSIR(-/-)小鼠中发现了一些与银屑病相关的新基因。结论：我们展示了VSIR(-/-)银屑病小鼠皮肤免疫细胞的全面单细胞图谱。这些史无前例的数据揭示了银屑病皮肤巨噬细胞的转录格局和表型异质性，并确定了它们的基因表达特征，表明VsiR(-/-)小鼠具有特殊的功能。我们的发现将为研究Vista在驱动牛皮癣中的作用提供新的机会。
Rationale: V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule. Vsir(-/-) mice have exacerbated psoriasis-like skin inflammation. The immune cell subsets involved in inflammation in Vsir(-/-) psoriatic mice are largely unknown. We have used scRNA-seq as an unbiased profiling strategy to study the heterogeneity of immune cells at a single cell level in the skin of Vsir(-/-) psoriatic mice.Methods: In the present study, the right ear and shaved back skin of wild type and Vsir(-/-) mice were treated with IMQ for 5 consecutive days to induce psoriasis-like dermatitis. Then, the single-cell RNA sequencing analysis of mouse back skin lesions was performed using 10 x Genomics technique.Results: We identified 12 major cell subtypes among 23,258 cells. The major populations of the skin cells included macrophages, dendritic cells and fibroblasts. Macrophages constituted the main immune cell population in the WT (61.29%) and Vsir(-/-) groups (77.7%). It should be noted that DCs and fibroblasts were expanded in the Vsir(-/-) psoriatic mice. Furthermore, the gene expression signatures were assessed. We observed that Hspb1 and Cebpb were significantly upregulated in the Vsir(-/-) psoriatic mice. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these subsets and uncovered putative functions of each cell type. Date analysis resulted in the discovery of a number of novel psoriasis-associated genes in Vsir(-/-) mice.Conclusion: We present a comprehensive single-cell landscape of the skin immune cells in Vsir(-/-) psoriatic mice. These unprecedented data uncovered the transcriptional landscape and phenotypic heterogeneity of skin macrophages in psoriasis and identified their gene expression signature suggesting specialized functions in Vsir(-/-) mice. Our findings will open novel opportunities to investigate the role of VISTA in driving psoriasis.