Identification of chondrocyte subpopulations in osteoarthritis using single-cell sequencing analysis.

ABSTRACT

Osteoarthritis (OA) is the most common joint disease. Previous studies were focused on general functions of chondrocyte population in OA without elucidating the existence of chondrocyte subpopulations. To investigate the heterogeneity of chondrocyte, here we conducted detailed analysis on the single-cell sequencing data of cartilage cells from OA patients. After quality control, unsupervised K-mean clustering identified seven different subpopulations of chondrocytes in OA. Those subpopulations of chondrocytes were nominated based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis: stress-metabolizing chondrocytes (cluster 1), rhythmic chondrocytes (cluster 2), apoptotic chondrocytes (cluster 3), matrix-synthesis-related chondrocytes (cluster 4), developmental chondrocytes (cluster 5), protein-synthesis-related chondrocytes (cluster 6 and 8), and osteogenesis chondrocytes (cluster 7). We further noticed that the stress-metabolizing chondrocytes (cluster 1) were dominant in early stages of cartilage damage with increased metabolic levels inhibiting cartilage tissue degeneration, while the matrix-synthesis-related chondrocytes (cluster 4) were mainly existed in the late stages of cartilage damage which reorganized collagen fibers with type III collagen disrupting the extracellular matrix and further cartilage damages. Besides, we identified genes NFKBIA and TUBB2B as potential markers for the stress-metabolizing chondrocytes and the matrix synthesis related chondrocytes, respectively. Our study identifies different chondrocyte subpopulations in OA, and highlights the potential different functions of chondrocyte subpopulations in the early versus late stages of cartilage damage.