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Different Molecular Features of Epithelioid and Giant Cells in Foreign Body Reaction Identified by Single-Cell RNA Sequencing

  • Author Footnotes
    8 These authors contributed equally to this work.
    Yoon-Seob Kim
    Footnotes
    8 These authors contributed equally to this work.
    Affiliations
    Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    IRCGP, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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  • Author Footnotes
    8 These authors contributed equally to this work.
    Sun Shin
    Footnotes
    8 These authors contributed equally to this work.
    Affiliations
    Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    IRCGP, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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  • Eun Ji Choi
    Affiliations
    Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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  • Seong Won Moon
    Affiliations
    Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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  • Chan Kwon Jung
    Affiliations
    Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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  • Author Footnotes
    9 These authors contributed equally to this work.
    Yeun-Jun Chung
    Footnotes
    9 These authors contributed equally to this work.
    Affiliations
    Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    IRCGP, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    9 These authors contributed equally to this work.
    Sug Hyung Lee
    Correspondence
    Correspondence: Sug Hyung Lee, Department of Pathology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
    Footnotes
    9 These authors contributed equally to this work.
    Affiliations
    Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    8 These authors contributed equally to this work.
    9 These authors contributed equally to this work.
      Although macrophage‒epithelioid cell (EPC)‒giant cell (GC) differentiation is acknowledged in foreign body reaction (FBR), the exact molecular features remain elusive. To discover the molecular profiles of EPC and GC, we analyzed mouse sponge and silk FBRs by integrating single-cell RNA sequencing and spatial sequencing, which identified seven cell types, including macrophages and fibroblasts. Macrophages comprised three subsets with a trajectory from M2-like cell to EPC to GC. They were different in many aspects, including cytokine, extracellular matrix organization/degradation, epithelial modules, and glycolysis that were consistent in both sponge and silk FBRs. EPCs exhibited epithelial modules and extracellular matrix organization, and GCs showed glycolysis, extracellular matrix degradation, and cell fusion signatures. Cellular interactions in GCs and M2-like cells were predicted to be higher than that in EPCs. High expression of inflammation or fusion-related (GPNMB, matrix metalloproteinase 12 gene MMP12, DCSTAMP) and glycolysis-related (PGAM1, ALDOA) genes was identified in GCs of human/mouse tissues, suggesting them as GC-specific markers. Our study identified unique signatures of EPCs and GCs in FBR. Importantly, GCs showed strong glycolysis signatures and cellular interactions, suggesting their activation in FBR. Our data on EPC and GC refinement and GC-specific markers enable the understanding of FBR and help to explore preventive and therapeutic management strategies for skin FBRs.

      Abbreviations:

      DEG (differentially expressed gene), ECM (extracellular matrix), EPC (epithelioid cell), FB (foreign body), FBR (foreign body reaction), GC (giant cell), MMP (matrix metalloproteinase), scRNA-seq (single-cell RNA sequencing)
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