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单细胞测序揭示了骨关节炎发展的潜在发病机制。

Single cell sequencing revealed the underlying pathogenesis of the development of osteoarthritis.

机构信息

Rheumatology Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China.

出版信息

Gene. 2020 Oct 5;757:144939. doi: 10.1016/j.gene.2020.144939. Epub 2020 Jul 5.

Abstract

Osteoarthritis (OA) is a chronic degenerative change with high incidence and leads to a lower quality of life and a larger socioeconomic burden. This study aimed to explore potential crucial genes and pathways associated with OA that can be used as potential biomarkers forearly treatment. Single-cell gene expression profile of 1464 chondrocytes and 192 fibroblasts in OA were downloaded from the public database (GSE104782 and GSE109449) for subsequent analysis. A total of eight clusters in chondrocytes and three clusters in fibroblasts of OA were identified using the Seurat pipeline and the "SingleR" package for cell-type annotation. Moreover, 44 common marker-genes between fibroblastic-like chondrocytes and fibroblasts were identified and the focal adhesions pathway was further identified as a significant potential mechanism of OA via functional enrichment analysis. Further, the reverse transcription quantitative real-time PCR (RT-qPCR) experiments at tissue's and cellular level confirmed that two key marker-genes (COL6A3 and ACTG1) might participate in the progression of OA. Summarily, we inferred that chondrocytes in OA might up-regulate the expression of COL6A3 and ACTG1 to complete fibroblasts transformation through the focal adhesion pathway. These findings are expected to gain a further insight into the development of OA fibrosis process and provide a promising target for treatment for early OA.

摘要

骨关节炎(OA)是一种具有高发病率的慢性退行性病变,导致生活质量下降和更大的社会经济负担。本研究旨在探索与 OA 相关的潜在关键基因和途径,可作为早期治疗的潜在生物标志物。从公共数据库(GSE104782 和 GSE109449)下载了 1464 个软骨细胞和 192 个成纤维细胞的单细胞基因表达谱,用于后续分析。使用 Seurat 管道和“SingleR”包对软骨细胞中的 8 个簇和成纤维细胞中的 3 个簇进行细胞类型注释。此外,还鉴定了成纤维细胞样软骨细胞和成纤维细胞之间的 44 个共同标记基因,并通过功能富集分析进一步确定了粘着斑途径是 OA 的一个重要潜在机制。此外,在组织和细胞水平的逆转录定量实时 PCR(RT-qPCR)实验证实,两个关键标记基因(COL6A3 和 ACTG1)可能参与 OA 的进展。总之,我们推断 OA 中的软骨细胞可能通过粘着斑途径上调 COL6A3 和 ACTG1 的表达,从而完成成纤维细胞的转化。这些发现有望深入了解 OA 纤维化过程的发展,并为早期 OA 的治疗提供有前途的靶点。

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