Single-cell transcriptomics reveals heterogeneity and intercellular crosstalk in human intervertebral disc degeneration

Dandan Wang; ZiZhang Li; Weimin Huang; Shengnan Cao; Liangyu Xie; Yuanzhen Chen; Huazhong Li; Lei Wang; Xiaoshu Chen; Jian-Rong Yang

doi:10.1016/j.isci.2023.106692

Single-cell transcriptomics reveals heterogeneity and intercellular crosstalk in human intervertebral disc degeneration

iScience. 2023 Apr 19;26(5):106692. doi: 10.1016/j.isci.2023.106692. eCollection 2023 May 19.

Authors

Dandan Wang¹, ZiZhang Li², Weimin Huang³, Shengnan Cao⁴, Liangyu Xie⁴, Yuanzhen Chen⁴, Huazhong Li⁴, Lei Wang³, Xiaoshu Chen⁵, Jian-Rong Yang²

Affiliations

¹ College of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, China.
² Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
³ 960th Hospital of PLA, Jinan 250031, China.
⁴ Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Jinan 250062, China.
⁵ Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

Abstract

The complexity of the human intervertebral disc (IVD) has hindered the elucidation of the microenvironment and mechanisms underlying IVD degeneration (IVDD). Here we determined the landscapes of nucleus pulposus (NP), annulus fibrosus (AF), and immunocytes in human IVD by scRNA-seq. Six NP subclusters and seven AF subclusters were identified, whose functional differences and distribution during different stages of degeneration (Pfirrmann I-V) were investigated. We found MCAM⁺ progenitor in AF, as well as CD24⁺ progenitor and MKI67⁺ progenitor in NP, forming a lineage trajectory from CD24⁺/MKI67⁺ progenitors to EffectorNP_⅓ during IVDD. There is a significant increase in monocyte/macrophage (Mφ) in degenerated IVDs (p = 0.044), with Mφ-SPP1 exclusively found in IVDD but not healthy IVDs. Further analyses of the intercellular crosstalk network revealed interactions between major subpopulations and changes in the microenvironment during IVDD. Our results elucidated the unique characteristics of IVDD, thereby shedding light on therapeutic strategies.

Keywords: Biopsy sample; Specialized functions of cells; Transcriptomics.