Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages.

Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages.
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全面的批量和单细胞转录组分析为了解骨关节炎相关滑膜巨噬细胞的特征提供了有用的见解

DOI:
10.3389/fimmu.2022.1078414
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发表时间:
2022
影响因子:
7.3
通讯作者:
Fan, Xiaoqin
Fan, Xiaoqin
中科院分区:
医学2区
文献类型:
--
作者:
Liao, Shengyou;Yang, Ming;Li, Dandan;Wu, Ye;Sun, Hong;Lu, Jingxiao;Liu, Xinying;Deng, Tingting;Wang, Yujie;Xie, Ni;Tang, Donge;Nie, Guohui;Fan, Xiaoqin

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骨关节炎(OA)是一种常见的慢性关节疾病,但分子和细胞事件与OA发病过程之间的关系仍不清楚。该研究旨在确定 OA 滑膜免疫浸润过程中的关键分子和细胞事件,并提供潜在的诊断和治疗靶点。为了识别 OA 中常见的差异表达基因并进行功能分析,我们比较了正常样本和 OA 样本之间的表达,并分析了蛋白质-蛋白质相互作用 (PPI)。此外,还利用免疫浸润分析探讨常见免疫细胞类型的差异,并利用基因集变异分析(GSVA)分析OA与正常组之间的通路状态。此外,通过最小绝对收缩和选择算子 (LASSO) 模型确定了 OA 的最佳诊断生物标志物。最后,通过单细胞和Scissor分析讨论了生物标志物在OA滑膜炎微环境中的关键作用。共鉴定出172个与骨关节滑膜炎相关的DEG(差异表达基因),这些基因主要丰富了8个功能类别。此外,免疫浸润分析发现巨噬细胞、B细胞记忆、B细胞和肥大细胞四种免疫细胞类型与OA显着相关,LASSO分析显示巨噬细胞是OA免疫浸润的最佳诊断生物标志物。此外,利用scRNA-seq数据集,我们还分析了OA滑膜炎症微环境中巨噬细胞的细胞通讯模式,发现CCL、MIF和TNF信号通路是主要的细胞通讯通路。最后,Scissor分析鉴定出CD163和LYVE1高表达的M2样巨噬细胞群,具有很强的抗炎能力,表明TNF基因可能在OA滑膜微环境中发挥重要作用。总体而言,巨噬细胞是骨关节滑膜炎免疫浸润的最佳诊断标志物,其在微环境中主要通过CCL、TNF和MIF信号通路与其他细胞进行通讯。此外,TNF基因可能在滑膜炎的发生发展中发挥重要作用。
Osteoarthritis (OA) is a common chronic joint disease, but the association between molecular and cellular events and the pathogenic process of OA remains unclear. The study aimed to identify key molecular and cellular events in the processes of immune infiltration of the synovium in OA and to provide potential diagnostic and therapeutic targets. To identify the common differential expression genes and function analysis in OA, we compared the expression between normal and OA samples and analyzed the protein–protein interaction (PPI). Additionally, immune infiltration analysis was used to explore the differences in common immune cell types, and Gene Set Variation Analysis (GSVA) analysis was applied to analyze the status of pathways between OA and normal groups. Furthermore, the optimal diagnostic biomarkers for OA were identified by least absolute shrinkage and selection operator (LASSO) models. Finally, the key role of biomarkers in OA synovitis microenvironment was discussed through single cell and Scissor analysis. A total of 172 DEGs (differentially expressed genes) associated with osteoarticular synovitis were identified, and these genes mainly enriched eight functional categories. In addition, immune infiltration analysis found that four immune cell types, including Macrophage, B cell memory, B cell, and Mast cell were significantly correlated with OA, and LASSO analysis showed that Macrophage were the best diagnostic biomarkers of immune infiltration in OA. Furthermore, using scRNA-seq dataset, we also analyzed the cell communication patterns of Macrophage in the OA synovial inflammatory microenvironment and found that CCL, MIF, and TNF signaling pathways were the mainly cellular communication pathways. Finally, Scissor analysis identified a population of M2-like Macrophages with high expression of CD163 and LYVE1, which has strong anti-inflammatory ability and showed that the TNF gene may play an important role in the synovial microenvironment of OA. Overall, Macrophage is the best diagnostic marker of immune infiltration in osteoarticular synovitis, and it can communicate with other cells mainly through CCL, TNF, and MIF signaling pathways in microenvironment. In addition, TNF gene may play an important role in the development of synovitis.
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