Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (1): 93-99.doi: 10.12307/2023.768

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Single-cell RNA sequencing and the pathogenesis of intervertebral disc degeneration

Cheng Haotian, Zhao Xiaofeng, Lu Xiangdong, Zhao Yibo, Fan Zhifeng, Qi Detai, Wang Xiaonan, Zhou Runtian, Jin Xinjie, Zhao Bin   

  1. Second Clinical Medical College of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2022-10-13 Accepted:2022-12-24 Online:2024-01-08 Published:2023-06-28
  • Contact: Zhao Bin, MD, Chief physician, Second Clinical Medical College of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • About author:Cheng Haotian, Master candidate, Second Clinical Medical College of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Supported by:
    Shanxi Provincial Special Project for the Transformation and Guidance of Scientific and Technological Achievements, No. 201904D121008 (to ZB)

Abstract: BACKGROUND: Intervertebral disc degeneration is clinically considered to be the main cause of low back pain, but due to the unclear pathogenesis of intervertebral disc degeneration, there is still a lack of effective means to delay the progression of the disease. Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level, reveal the gene expression intensity of a single cell, discover different cell subsets in tissues according to the heterogeneity of cells, study the pathogenesis of intervertebral disc degeneration at the molecular level, and provide a new theoretical basis for its early diagnosis and treatment.
OBJECTIVE: To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years.
METHODS: A computer was used to search PubMed, Web of Science, CNKI and WanFang databases for the literature published from 2012 to 2022. Key words were “single-cell RNA sequencing, intervertebral disc degeneration, sequencing Technology” in Chinese and English. Duplicate, poor-quality and irrelevant articles were excluded; a total of 70 articles were eventually included. 
RESULTS AND CONCLUSION: (1) We identified new cell subsets such as homeostatic chondrocytes, hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells, identified the marker genes and transcription factors of these cell subsets, and described the functions, differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration, and proposed the concept of progenitor nucleus pulposus cells. A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice. (2) Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified, and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro. Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix, and was remarkably effective in the treatment of intervertebral disc degeneration. (3) Regulatory chondrocytes were found in endplate cartilage. Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified. Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis. (4) Immune cells such as macrophages, T cells, myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues, demonstrating the existence of immune response during intervertebral disc degeneration. It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes, and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.

Key words: single-cell RNA sequencing, intervertebral disc degeneration, pathogenesis, sequencing technology

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