Single-cell sequencing reveals cellular heterogeneity of nucleus pulposus in intervertebral disc degeneration

作者：Shu Jia, Hongmei Liu, Tao Yang, Sheng Gao, Dongru Li, Zhenyu Zhang, Zifang Zhang, Xu Gao, Yanhu Liang, Xiao Liang, Yexin Wang, Chunyang Meng · 发表于：Scientific Reports · 年份：2024 · DOI：10.1038/s41598-024-78675-x · 被引用次数：26 · 研究领域：Spine and Intervertebral Disc Pathology、Musculoskeletal pain and rehabilitation、Osteoarthritis Treatment and Mechanisms

The nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in NP tissue during IVDD progression. However, the cellular and molecular alterations of diverse cell clusters during IVDD remain to be fully elucidated. NP tissues were isolated from patients with different grades of IVDD undergoing discectomy, and then subjected to single-cell RNA sequencing (scRNA-seq). Cell subsets were identified based on unbiased clustering of gene expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the molecular features of diverse cell clusters. Monocle analysis was used to illustrate the differentiation trajectories of chondrocytes. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocytes and other cells during IVDD. Based on the expression profiles of 47,610 individual cells, eight putative clusters including chondrocytes, endothelial cells, fibroblasts, macrophages, mural cells, osteoclasts, proliferating stromal cells and T cells were identified. The chondrocyte cluster was classified into three subsets, C1-C3, which were associated with stress-resistance, fibrosis and inflammatory responses, respectively. Pseudo-time trajectories suggested that chondrocytes gradually differentiated into fibroblasts during IVDD. Immune cells including cDC2s, macrophages and monocytes were identified. Further an...