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利用单细胞RNA测序技术鉴定人骨关节炎中软骨细胞的细胞异质性和免疫原性

Identification of cellular heterogeneity and immunogenicity of chondrocytes single-cell RNA sequencing technique in human osteoarthritis.

作者信息

Hu Xinyue, Li Zhuang, Ji Mingliang, Lin Yucheng, Chen Yuzhi, Lu Jun

机构信息

School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

出版信息

Front Pharmacol. 2022 Sep 29;13:1004766. doi: 10.3389/fphar.2022.1004766. eCollection 2022.

DOI:10.3389/fphar.2022.1004766
PMID:36249797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9562112/
Abstract

Osteoarthritis (OA) has placed a heavy burden to the economy and humanistics. To explore the biological functions and markers of chondrocytes contributes significantly to the accurate diagnosis and targeted treatment of OA. We systematically analyzed the immunogenicity and biological function of varied chondrocytes at single cell resolution, and identified the chondrocyte subtypes and biomarkers involved in the development of OA, which are verified in the bulk sequencing cohort. Based on previous study, we defined eight subtypes of chondrocytes with different biological functions, finding out that effector chondrocytes (ECs) and fibrocartilage chondrocytes (FCs) may promote the development of OA. Compared with other chondrocytes, ECs and FCs show stronger immunogenicity. FCs mainly affects the degeneration of cartilage caused by fibrous degeneration, while ECs mainly exerts immune function and causes tissues inflammation. In addition, the canonical gene markers of EC and FC assist with the prediction of OA, which has been verified in Bulk RNA sequencing data from two GEO datasets. In summary, this study provides a new perspective for the exploration of cellular heterogeneity and pathophysiology in OA and will make contribution to the accurate diagnosis and targeted treatment of OA.

摘要

骨关节炎（OA）给经济和人文领域带来了沉重负担。探索软骨细胞的生物学功能和标志物对OA的准确诊断和靶向治疗具有重要意义。我们在单细胞分辨率下系统分析了不同软骨细胞的免疫原性和生物学功能，鉴定出参与OA发展的软骨细胞亚型和生物标志物，并在批量测序队列中进行了验证。基于先前的研究，我们定义了具有不同生物学功能的八种软骨细胞亚型，发现效应软骨细胞（ECs）和纤维软骨细胞（FCs）可能促进OA的发展。与其他软骨细胞相比，ECs和FCs表现出更强的免疫原性。FCs主要影响纤维变性引起的软骨退变，而ECs主要发挥免疫功能并导致组织炎症。此外，EC和FC的典型基因标志物有助于OA的预测，这已在两个GEO数据集的批量RNA测序数据中得到验证。总之，本研究为探索OA中的细胞异质性和病理生理学提供了新视角，将为OA的准确诊断和靶向治疗做出贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2407/9562112/e63e4ceb9a55/fphar-13-1004766-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2407/9562112/e63e4ceb9a55/fphar-13-1004766-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2407/9562112/6b1b18112231/fphar-13-1004766-g001.jpg
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