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
Affiliations
Dandan Wang
College of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, China; Corresponding author
ZiZhang Li
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Weimin Huang
960th Hospital of PLA, Jinan 250031, China
Shengnan Cao
Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Jinan 250062, China
Liangyu Xie
Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Jinan 250062, China
Yuanzhen Chen
Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Jinan 250062, China
Huazhong Li
Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Jinan 250062, China
Lei Wang
960th Hospital of PLA, Jinan 250031, China
Xiaoshu Chen
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author
Jian-Rong Yang
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author
Summary: 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.
