整合单细胞RNA测序和GWAS数据识别骨关节炎相关细胞型研究  

Integrating single-cell RNA sequencing and genome-wide association study data identifies osteoarthritis-associated cell types

作　　者：彭俊[1] 王强[1] 江龙[1] 黄晨程 杨斐 史智伟[1] 葛弛 黄鹏 PENG Jun;WANG Qiang;JIANG Long;HUANG Chen-cheng;YANG Fei;SHI Zhi-wei;GE Chi;HUANG Peng(Yixing Municipal People′s Hospital,Wuxi Jiangsu 214200,China;不详)

机构地区：[1]宜兴市人民医院,江苏无锡214200 [2]南京医科大学

出　　处：《江苏预防医学》2024年第2期156-160,共5页Jiangsu Journal of Preventive Medicine

摘　　要：目的采用单细胞RNA测序(ScRNA-seq)的分子程序和谱系进展模式,研究人类骨关节炎发病机制。方法共收集7410例骨关节炎患者和11009名健康对照人群的关节滑膜组织数据,并进行组织学测定、无偏的全转录组ScRNA-seq分析和计算分析。研究骨关节炎的转录程序与临床结果之间的相互关系,利用R软件Seurat包进行质控、降维、细胞分群、注释细胞类型、提取高表达基因等过程。对全基因组关联分析(GWAS)数据集用R软件整理成summary_statistics文件类型,进行连锁不平衡回归(ldsc)分析。结果通过对骨关节炎细胞分群并注释得到7个界定的软骨细胞群,分别是增殖软骨细胞(proliferative chondrocyte,ProC)、前肥大软骨细胞(prehypertrophic chondrocytespre,preHTC)、肥大软骨细胞(hypertrophic chon-drocyte,HTC)、纤维软骨细胞(fibrocartilage chondrocytes,FC)、效应软骨细胞(effector chondrocyte,EC)、调节软骨细胞(regulatory chondrocyte,RegC)和稳态软骨细胞(homeostatic chondrocyte,HomC)。使用计算分析证明软骨细胞与骨关节炎之间的关系,其P值分别是0.035、0.041、0.082、0.182、0.266、0.394、0.572。逐步推导出临床结果的预判目标,阐释多种不同细胞类别在骨关节炎初期诊断和诊治中的作用。结论本研究结果为软骨细胞分类提供了新的见解,并为骨关节炎软骨再生提供了潜在线索。Objective To investigate the pathogenesis of human osteoarthritis using the molecular program and lineage progression of single-cell RNA sequencing(scRNA-seq).Methods Data pertaining to joint synovial tissues were captured from 7410 osteoarthritis patients and 11009 healthy controls,and joint synovial tissues were subjected to histological examinations,unbiased full-length transcriptome scRNA-seq analysis and computational analysis.The correlation between transcriptome program and clinical out-comes was examined.Quality control,dimensionality reduction,cell clustering,annotation of cell types and extraction of highly expressed genes were performed using the Seurat package in the R software.The genome-wide association study datasets were formatted into sum-mary_statistics files using the R software,and linkage disequilibrium score regression was performed.Results Osteoarthritis cell clus-ters were annotated to seven defined chondrocyte populations,including proliferative chondrocytes,prehypertrophic chondrocytes,hyper-trophic chondrocytes,fibrocartilage chondrocytes,effector chondrocytes,regulatory chondrocytes and homeostatic chondrocytes.Computa-tional analysis revealed significant associations of proliferative chondrocytes(P=0.035)and prehypertrophic chondrocytes with osteo-arthritis(P=0.041),and no associations of hypertrophic chondrocytes(P=0.082),fibrocartilage chondrocytes(P=0.182),effector chondrocytes(P=0.266),regulatory chondrocytes(P=0.394)or homeostatic chondrocytes with osteoarthritis(P=0.572).The an-ticipating targets of clinical outcomes were gradually deduced,and the roles of different cell types in initial diagnosis and diagnosis and treatment of osteoarthritis were unraveled.Conclusions The results provide new insights into chondrocyte classification and potential clues for cartilage regeneration in human osteoarthritis,which is promising for improving human health in the future.

关 键 词：骨关节炎 微小RNA 调控网络 生物信息学 软骨破坏 

分 类 号：R681[医药卫生—骨科学]