Single-cell transcriptomic profiling of lung fibroblasts in a bleomycin-induced systemic sclerosis mouse model.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Bleomycin*/toxicity ; Fibroblasts*/metabolism ; Fibroblasts*/pathology ; Fibroblasts*/drug effects ; Scleroderma, Systemic*/pathology ; Scleroderma, Systemic*/genetics ; Scleroderma, Systemic*/chemically induced ; Scleroderma, Systemic*/metabolism ; Disease Models, Animal* ; Single-Cell Analysis* ; Lung*/pathology ; Lung*/metabolism ; Gene Expression Profiling* ; Pulmonary Fibrosis*/chemically induced ; Pulmonary Fibrosis*/genetics ; Pulmonary Fibrosis*/pathology ; Pulmonary Fibrosis*/metabolism; Animals ; Mice ; Transcriptome ; Mice, Inbred C57BL ; Female
    • Abstract:
      Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, vascular abnormalities, and immune dysfunction, with no definitive cure. Patients with progressive pulmonary fibrosis face a high mortality risk, underscoring the urgent need for effective treatments. Although fibroblasts are recognized as key drivers of fibrosis, the precise molecular mechanisms remain poorly understood. In this study, we employ single-cell RNA sequencing to explore the role of fibroblasts in pulmonary fibrosis. Using a mouse model induced by subcutaneous bleomycin administration, we identify two distinct fibroblast subpopulations: nephronectin-positive (NPNT) and peptidase inhibitor 16-positive cells(PI16). NPNT-positive fibroblasts, located around the alveoli, exhibit increased extracellular matrix expression following bleomycin treatment. To further understand pulmonary fibrosis, subcutaneous and intratracheal bleomycin-induced mouse models are compared. A comparative gene expression analysis reveals shared and unique features between the models, highlighting the complexity of the fibrotic process. These findings offer valuable insights into the molecular mechanisms of SSc-associated pulmonary fibrosis and may inform the development of therapies targeting specific fibroblast subpopulations or pathways.
      Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Katsuto Tamai is a scientific founder of and received research funding from StemRIM. Katsuto Tamai and Takashi Shimbo are StemRIM stockholders. Yuya Ouchi, Tomomi Kitayama, Sho Yamazaki and Kastuto Tamai are employees of StemRIM.
      (Copyright © 2024. Published by Elsevier Inc.)
    • Contributed Indexing:
      Keywords: Bleomycin-induced SSc mouse model; Nephronectin; Peptidase inhibitor 16; Pulmonary fibrosis; Single-cell RNA sequencing; Systemic sclerosis
    • Accession Number:
      11056-06-7 (Bleomycin)
    • Publication Date:
      Date Created: 20241128 Date Completed: 20241209 Latest Revision: 20241209
    • Publication Date:
      20241210
    • Accession Number:
      10.1016/j.bbrc.2024.151017
    • Accession Number:
      39608052