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Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing

  • Author Footnotes
    a ZeYu Huang and ZeYu Luo contributed equally to this work.
    Z.Y. Huang
    Footnotes
    a ZeYu Huang and ZeYu Luo contributed equally to this work.
    Affiliations
    Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, PR China

    Department of Orthopaedic Surgery, School of Medicine, Duke University, Durham, NC, USA
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  • Author Footnotes
    a ZeYu Huang and ZeYu Luo contributed equally to this work.
    Z.Y. Luo
    Footnotes
    a ZeYu Huang and ZeYu Luo contributed equally to this work.
    Affiliations
    Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, PR China
    Search for articles by this author
  • Y.R. Cai
    Affiliations
    Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, PR China
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  • C.-H. Chou
    Affiliations
    Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
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  • M.L. Yao
    Affiliations
    Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, PR China
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  • F.X. Pei
    Affiliations
    Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, PR China
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  • V.B. Kraus
    Correspondence
    Address correspondence and reprint requests to: V.B. Kraus, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
    Affiliations
    Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA

    Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
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  • Z.K. Zhou
    Correspondence
    Address correspondence and reprint requests to: Z.K. Zhou, Chair Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, 37# Wainan Guoxue Road, Chengdu, Sichuan Province, PR China. Tel: 86-18980601028; Fax: 86-028-85423848.
    Affiliations
    Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, PR China
    Search for articles by this author
  • Author Footnotes
    a ZeYu Huang and ZeYu Luo contributed equally to this work.
Published:December 28, 2021DOI:https://doi.org/10.1016/j.joca.2021.12.007

      Summary

      Objectives

      To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses.

      Methods

      OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium.

      Results

      We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an “arthritis” specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively.

      Conclusion

      This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.

      Keywords

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