A Single-Cell RNA-Sequencing Analysis of Distinct Subsets of Synovial Macrophages in Rheumatoid Arthritis.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiaoyu Li, Hao Sun, Hao Li, Deng Li, Zhiqing Cai, Jie Xu, Ruofan Ma
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引用次数: 3

Abstract

The polarization states and molecular signatures of macrophages in the synovium of patients with rheumatoid arthritis (RA) are not well understood. We aimed to identify specific subpopulations of macrophages and their features in RA synovium thereby providing a theoretical basis for treatment of RA. Single-cell RNA sequencing (scRNA-seq) was used to identify cell subsets and their gene signatures in synovial cells of patients with RA and osteoarthritis (OA). Spatial distribution of macrophages was visualized by deconvolving spatial transcriptomic data with scRNA-seq data. Flow cytometry and immunofluorescence were applied to investigate the expression of macrophage polarization indicators CD86 and CD206. Trajectory analysis was used to determine differentiation relationships. Transcription factor (TF) analysis was performed to find specific TFs. scRNA-seq identified three cell clusters of macrophages: M0-like MARCO+ Mϕ1, M2-like CSF1R+ Mϕ2, and M1-like PLAUR+ Mϕ3. Mϕ1 distributed widely in the synovium, whereas Mϕ2 and Mϕ3 distributed sparsely. CD86 and CD206 were both upregulated in macrophages of RA synovium, especially in lining layer. Trajectory analysis showed that Mϕ1 existed at the start of the differentiation trajectory. HOXB6, STAT1, and NFKB2 were TFs specific to Mϕ1, Mϕ2, and Mϕ3 under RA condition, respectively. Compared with in OA condition, three macrophage clusters upregulated CXCL2, CXCL1, IL1B, TNFAIP3, ICAM1, CXCL3, PLAU, CCL4L2, CCL4, and TNF in NF-kappa B signaling pathway. The identification of macrophage subsets with different polarized states and their molecular signatures provided a more precise understanding of macrophages, which may contribute to the development of novel therapeutic strategy for RA.

类风湿关节炎滑膜巨噬细胞不同亚群的单细胞rna测序分析。
类风湿性关节炎(RA)患者滑膜中巨噬细胞的极化状态和分子特征尚不清楚。我们旨在确定RA滑膜中巨噬细胞的特定亚群及其特征,从而为RA的治疗提供理论基础。单细胞RNA测序(scRNA-seq)用于鉴定RA和骨关节炎(OA)患者滑膜细胞中的细胞亚群及其基因特征。通过将空间转录组数据与scRNA-seq数据进行反卷积,可以可视化巨噬细胞的空间分布。采用流式细胞术和免疫荧光法检测巨噬细胞极化指标CD86和CD206的表达。轨迹分析用于确定分化关系。转录因子(TF)分析找到特异性的TF。scRNA-seq鉴定了三种巨噬细胞簇:m0样MARCO+ Mϕ1, m2样CSF1R+ Mϕ2和m1样PLAUR+ Mϕ3。m_1广泛分布于滑膜内,而m_2和m_2则稀疏分布。RA滑膜巨噬细胞中CD86和CD206均表达上调,尤其是在粘膜层。轨迹分析表明,在分化轨迹开始时,存在着m.d. 1。HOXB6、STAT1和NFKB2分别是RA条件下对Mϕ1、Mϕ2和Mϕ3特异性的tf。与OA组相比,三个巨噬细胞簇上调NF-kappa B信号通路中的CXCL2、CXCL1、IL1B、TNFAIP3、ICAM1、CXCL3、PLAU、CCL4L2、CCL4和TNF。鉴别不同极化状态的巨噬细胞亚群及其分子特征,有助于更准确地了解巨噬细胞,这可能有助于开发新的RA治疗策略。
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来源期刊
DNA and cell biology
DNA and cell biology 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
93
审稿时长
1.5 months
期刊介绍: DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward. DNA and Cell Biology coverage includes: Gene Structure, Function, and Regulation Gene regulation Molecular mechanisms of cell activation Mechanisms of transcriptional, translational, or epigenetic control of gene expression Molecular Medicine Molecular pathogenesis Genetic approaches to cancer and autoimmune diseases Translational studies in cell and molecular biology Cellular Organelles Autophagy Apoptosis P bodies Peroxisosomes Protein Biosynthesis and Degradation Regulation of protein synthesis Post-translational modifications Control of degradation Cell-Autonomous Inflammation and Host Cell Response to Infection Responses to cytokines and other physiological mediators Evasive pathways of pathogens.
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