Integrating single-cell RNA sequencing and genome-wide association study data identifies osteoarthritis-associated cell types
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 7 410 osteoarthritis patients and 11 009 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.
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