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

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0426720 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1747 (Electronic) Linking ISSN: 0022202X NLM ISO Abbreviation: J Invest Dermatol Subsets: MEDLINE
    • Publication Information:
      Publication: 2016- : New York : Elsevier
      Original Publication: Baltimore, Williams & Wilkins.
    • Subject Terms:
      Foreign-Body Reaction*/genetics ; Foreign-Body Reaction*/metabolism ; Giant Cells*/metabolism; Animals ; Humans ; Mice ; Sequence Analysis, RNA ; Silk
    • Abstract:
      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.
      (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Accession Number:
      0 (Silk)
    • Publication Date:
      Date Created: 20220719 Date Completed: 20221125 Latest Revision: 20230104
    • Publication Date:
      20230104
    • Accession Number:
      10.1016/j.jid.2022.06.014
    • Accession Number:
      35853485