Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs
Yibo Gan,
Jian He,
Jun Zhu,
Zhengyang Xu,
Zhong Wang,
Jing Yan,
Ou Hu,
Zhijie Bai,
Lin Chen,
Yangli Xie,
Min Jin,
Shuo Huang,
Bing Liu,
Peng Liu
Affiliations
Yibo Gan
Department of Spine Surgery, Center of Orthopedics, Daping Hospital, Army Medical University (Third Military Medical University)
Jian He
State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences
Jun Zhu
Department of Spine Surgery, Center of Orthopedics, Daping Hospital, Army Medical University (Third Military Medical University)
Zhengyang Xu
State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences
Zhong Wang
Department of Spine Surgery, Center of Orthopedics, Daping Hospital, Army Medical University (Third Military Medical University)
Jing Yan
State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences
Ou Hu
Department of Spine Surgery, Center of Orthopedics, Daping Hospital, Army Medical University (Third Military Medical University)
Zhijie Bai
State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences
Lin Chen
Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Laboratory for the Prevention and Rehabilitation of Military Training Related Injuries, Daping Hospital, Army Medical University (Third Military Medical University)
Yangli Xie
Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Laboratory for the Prevention and Rehabilitation of Military Training Related Injuries, Daping Hospital, Army Medical University (Third Military Medical University)
Min Jin
Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Laboratory for the Prevention and Rehabilitation of Military Training Related Injuries, Daping Hospital, Army Medical University (Third Military Medical University)
Shuo Huang
Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Laboratory for the Prevention and Rehabilitation of Military Training Related Injuries, Daping Hospital, Army Medical University (Third Military Medical University)
Bing Liu
State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences
Peng Liu
Department of Spine Surgery, Center of Orthopedics, Daping Hospital, Army Medical University (Third Military Medical University)
Abstract A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development, homeostasis, and disease of human intervertebral disks (IVDs) remains challenging. Here, the transcriptomic landscape of 108 108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs, including the nucleus pulposus (NP), annulus fibrosus, and cartilage endplate (CEP). The chondrocyte subclusters were classified based on their potential regulatory, homeostatic, and effector functions in extracellular matrix (ECM) homeostasis. Notably, in the NP, a PROCR+ resident progenitor population showed enriched colony-forming unit-fibroblast (CFU-F) activity and trilineage differentiation capacity. Finally, intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-β cascades are important cues in the NP microenvironment. In conclusion, a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.
