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

• Published in: Biochemical and biophysical research communications 2024-12, Vol.741, p.151017, Article 151017
• Main Authors: Maekawa, Aya, Ueda-Hayakawa, Ikuko, Shimbo, Takashi, Yamazaki, Sho, Ouchi, Yuya, Kitayama, Tomomi, Tamai, Katsuto, Fujimoto, Manabu
• Format: Article
• Language: English
• Subjects: Animals; Bleomycin - toxicity; Bleomycin-induced SSc mouse model; Disease Models, Animal; Female; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Profiling; Lung - metabolism; Lung - pathology; Mice; Mice, Inbred C57BL; Nephronectin; Peptidase inhibitor 16; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Scleroderma, Systemic - chemically induced; Scleroderma, Systemic - genetics; Scleroderma, Systemic - metabolism; Scleroderma, Systemic - pathology; Single-Cell Analysis; Single-cell RNA sequencing; Systemic sclerosis; Transcriptome
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.151017

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. •Characterized two subpopulations based on the expression of Npnt and Pi16.•Npnt-positive fibroblasts exhibited increased ECM expression.•Bleomycin-induced lung fibrosis models showed both shared and distinct features.