Targeted biomarkers of single-cell RNA sequencing in intervertebral disc degeneration
BACKGROUND:Intervertebral disc degeneration is the most common cause of low back pain;however,its pathogenesis is not yet fully understood.Therefore,it is imperative to explore new strategies for the prevention and treatment of intervertebral disc degeneration.Single-cell RNA sequencing allows high-throughput sequencing of mRNAs at the single-cell level,revealing cell heterogeneity and specific subgroups.This technology provides deeper insights into the regulatory mechanisms of the development of intervertebral disc degeneration,enhances the identification of potential targets,and promotes the exploration of early diagnosis and treatment.OBJECTIVE:To understand single-cell RNA sequencing and its main processes,and to review the recent research progress in single-cell RNA sequencing in intervertebral disc degeneration over the past few years,exploring its potential applications in the discovery of targeted biomarkers.METHODS:A computerized search of relevant literature published from January 2014 to June 2024 in PubMed,Web of Science,CNKI,and WanFang databases was performed using the search terms"single-cell RNA sequencing,sequencing technology,intervertebral disc degeneration,nucleus pulposus,annulus fibrosus,cartilage endplate"in English and Chinese.A total of 57 articles were finally selected for relevant analysis after duplicate and irrelevant literature was excluded.RESULTS AND CONCLUSION:(1)Single-cell RNA sequencing has emerged as a powerful tool for studying gene expression at the single-cell level.It has identified new cell subpopulations and elucidated their functions in intervertebral disc degeneration,thereby enhancing our understanding of the pathological processes involved in this condition.Several new cell subpopulations in the nucleus pulposus have been identified,including hypertrophic cartilage-like nucleus pulposus cells,effector nucleus pulposus cells,and homeostatic nucleus pulposus cells.These findings elucidate the functions and differentiation pathways of these subpopulations during intervertebral disc degeneration,highlighting variations in their proportions and dominant groups at different stages of degeneration.New subpopulations of annulus fibrosus cells,including the Grem1+and Lum+subpopulations,have been discovered.Grem1+is a resident progenitor subpopulation in the annulus fibrosus,with Sox9 and Id1 as key regulatory factors involved in tissue development and cell differentiation.Nr2f2 and Creb5 may be responsible for the vascularization function of the Lum+subpopulation,providing potential cell sources and regulatory targets for the treatment and repair of intervertebral disc degeneration.(2)Mesenchymal chondrocytes found in the cartilage endplate can be further subdivided into homeostatic,effector,and regulatory subtypes.Homeostatic chondrocytes are primarily involved in ossification and collagen-binding processes,regulatory chondrocytes participate mainly in stimulatory and control responses,and effector chondrocytes are predominantly involved in metabolic processes.(3)Further enrichment of monocytes/macrophages in the immune cells of degenerating disc tissues into monocytes/macrophages for oxidative stress,activated tissues,and homeostasis has deepened the understanding of the different functions of monocyte/macrophage subpopulations during the progression of intervertebral disc degeneration to provide personalized treatments based on specific subpopulations.The review summarizes recent advances in single-cell RNA sequencing for identifying targeted biomarkers in intervertebral disc degeneration,offering new insights into diagnostic and therapeutic strategies.
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