Single-Cell Transcriptome Profiling Reveals Multicellular Ecosystem of Nucleus Pulposus during Degeneration Progression

Ji Tu; Wentian Li; Sidong Yang; Pengyi Yang; Qi Yan; Shenyu Wang; Kaitao Lai; Xupeng Bai; Cenhao Wu; Wenyuan Ding; Justin Cooper-White; Ashish Diwan; Cao Yang; Huilin Yang; Jun Zou

doi:10.1002/advs.202103631

Single-Cell Transcriptome Profiling Reveals Multicellular Ecosystem of Nucleus Pulposus during Degeneration Progression

Adv Sci (Weinh). 2022 Jan;9(3):e2103631. doi: 10.1002/advs.202103631. Epub 2021 Nov 26.

Authors

Ji Tu^{1

2}, Wentian Li², Sidong Yang^{3

4}, Pengyi Yang^{5

6

7}, Qi Yan¹, Shenyu Wang¹, Kaitao Lai^{8

9}, Xupeng Bai¹⁰, Cenhao Wu¹, Wenyuan Ding⁴, Justin Cooper-White^{3

11}, Ashish Diwan^{2

12}, Cao Yang¹³, Huilin Yang¹, Jun Zou¹

Affiliations

¹ Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
² Spine Labs, St. George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, 2217, Australia.
³ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Brisbane, Queensland, 4072, Australia.
⁴ Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 05000, China.
⁵ Charles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.
⁶ School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, 2006, Australia.
⁷ Computational Systems Biology Group, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, 2145, Australia.
⁸ The ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, 2139, Australia.
⁹ Concord Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2139, Australia.
¹⁰ Cancer Care Centre, St. George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, 2052, Australia.
¹¹ School of Chemical Engineering, The University of Queensland, Brisbane, Queensland, 4072, Australia.
¹² Spine Service, Department of Orthopaedic Surgery, St. George Hospital, Kogarah, New South Wales, 2217, Australia.
¹³ Department of Orthopaedic Surgery, Wuhan Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.

Abstract

Although degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, a comprehensive single-cell resolution transcript landscape of human NP is reported. Six novel human NP cells (NPCs) populations are identified by their distinct molecular signatures. The potential functional differences among NPC subpopulations are analyzed. Predictive transcripts, transcriptional factors, and signal pathways with respect to degeneration grades are explored. It is reported that fibroNPCs is the subpopulation for end-stage degeneration. CD90+NPCs are observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). Integrin αM (CD11b) and oxidized low density lipoprotein receptor 1 (OLR1) as surface markers of NP-derived G-MDSCs are uncovered. The G-MDSCs are found to be enriched in mildly degenerated (grade II and III) NP tissues compared to severely degenerated (grade IV and V) NP tissues. Their immunosuppressive function and alleviation effects on NPCs' matrix degradation are revealed in vitro. Collectively, this study reveals the NPC-type complexity and phenotypic characteristics in NP, thereby providing new insights and clues for IVDD treatment.

Keywords: intervertebral disc degeneration; low back pain; nucleus pulposus; single-cell RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Gene Expression Profiling / methods*
Humans
Intervertebral Disc / metabolism
Intervertebral Disc Degeneration / metabolism*
Intervertebral Disc Degeneration / physiopathology*
Male
Middle Aged
Nucleus Pulposus / metabolism*
Signal Transduction
Stem Cells / metabolism*

Abstract

Publication types

MeSH terms

Grants and funding