Open AccessSingle‐Cell Transcriptome Profiling Reveals Multicellular Ecosystem of Nucleus Pulposus during Degeneration Progression
Author(s) -
Tu Ji,
Li Wentian,
Yang Sidong,
Yang Pengyi,
Yan Qi,
Wang Shenyu,
Lai Kaitao,
Bai Xupeng,
Wu Cenhao,
Ding Wenyuan,
CooperWhite Justin,
Diwan Ashish,
Yang Cao,
Yang Huilin,
Zou Jun
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202103631
Subject(s) - biology , transcriptome , microbiology and biotechnology , cell , in vitro , progenitor cell , cancer research , stem cell , genetics , gene expression , gene
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 α M (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.