Single-cell RNA seq analysis identifies the biomarkers and differentiation of chondrocyte in human osteoarthritis

Abstract

Background： Single-cell RNA sequencing (scRNA-seq) was recently adopted for exploring molecular programmes and lineage progression patterns of pathogenesis of important diseases. In this study, scRNA-seq was used to identify potential markers for chondrocytes in osteoarthritis (OA) and to explore the function of different types of chondrocytes in OA.Methods：Here we aimed to identify the biomarkers and differentiation of chondrocyte by Single-cell RNA seq analysis. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify the function of candidate marker genes in chondrocytes. Protein–protein interaction (PPI) network was constructed to find the hub genes in 3 types of chondrocyte respectively. We also used qRT-PCR to detect the expression level of the candidate marker genes in different types of chondrocyte. Results： In this study, we characterized the single-cell expression profiling of 480 chondrocyte samples and found hypertrophic chondrocyte (HTC), homeostatic chondrocyte (HomC) and fibrocartilage chondrocyte (FC) respectively. The results of GO and KEGG analysis showed the candidate marker genes made specific function in these chondrocytes to regulate the development of OAs respectively. We further revealed the differential expression of top 10 marker genes in 3 types of chondrocyte. The marker genes of HTC and FC were mainly expressed in their cell subset respectively. The marker genes of HomC did not have obviously differential expression among different types of chondrocyte. Last, we predicted the key genes in each cell subset. CD44, JUN and FN1 were predicted tightly related to the proliferation and differentiation of chondrocytes in OAs and could be regarded as biomarkers to estimate the development of OA. Conclusion： Our results provide new insights into exploring the roles of different types of chondrocyte in OA. The biomarkers of chondrocyte were also valuable for estimating OA progression.

Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration

“…Collagen binding, ECM binding and structural ECM functions were previously reported following analysis of candidate marker genes of chondrocytes in human osteoarthritis reporting an enrichment of the molecular function of collagen binding. It has also previously been suggested that the integrin-binding sialoprotein (IBSP) interacts with collagen and appears to modulate cell-matrix interactions [ 113 , 114 ].…”

Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression

“…Single-cell RNA sequencing (scRNA-seq) has been applied for uncovering molecular programs and lineage progression of OA ( Zhang et al, 2020c ). For instance, Zhang et al (2020c) identified the biomarkers and differentiation of chondrocytes in human OA using scRNA-seq analyses.…”

“…Single-cell RNA sequencing (scRNA-seq) has been applied for uncovering molecular programs and lineage progression of OA ( Zhang et al, 2020c ). For instance, Zhang et al (2020c) identified the biomarkers and differentiation of chondrocytes in human OA using scRNA-seq analyses. Moreover, Ji et al (2019) adopted scRNA-seq analyses to reveal chondrocyte taxonomy and mechanisms of human OA cartilage regeneration.…”

Multi-omics molecular biomarkers and database of osteoarthritis

“…Recently, a breakthrough single-cell RNA-seq study revealed the progression of human OA by defining seven chondrocyte populations, including proliferative chondrocyte, prehypertrophic chondrocytes, hypertrophic chondrocytes (HTCs), fibrocartilage chondrocytes (FCs) and three novel populations with distinct functions ( 77 ). In another single-cell expression profiling research, HTC, homeostatic chondrocyte and FC were characterized in 480 chondrocyte samples ( 23 ). Furthermore, the study compared the transcriptional program and all major cell populations in patient groups between KBD and OA.…”