Single Cell <scp>RNA</scp>‐Seq Identifies Cell Subpopulations Contributing to Idiopathic Pulmonary Fibrosis in Humans

The cell populations, particularly subpopulations, involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) remain incompletely understood. This study employed single-cell RNA-seq to identify cell populations and subpopulations with significantly altered proportions in the lungs of patients with IPF. In IPF lungs, endothelial cell proportions were significantly increased, while alveolar epithelial cell proportions were markedly decreased. Among the three identified fibroblast subpopulations, the proportion of myofibroblasts was significantly increased, while the proportions of the other two fibroblast subtypes were reduced. Similarly, within the three macrophage subpopulations, the macrophage_SPP1 subpopulation, localised to fibroblastic foci, showed a significant increase in proportion, while the alveolar macrophage subpopulation was significantly reduced. Trajectory analysis revealed that fibroblasts in IPF lungs could differentiate into myofibroblasts, and alveolar macrophages could transition into the macrophage_SPP1 subpopulation. Among T-cell subpopulations, only the CD4 T_FOXP3 subpopulation exhibited a significant change, whereas all four B-cell subpopulations showed significant proportional shifts. These findings provide a comprehensive view of the cellular alterations contributing to IPF pathogenesis. Extensive interactions among various cell populations and subpopulations were identified. The proportions of various cell populations and subpopulations in IPF lungs, including endothelial cells, fibroblasts, macrophages and B cells, were significantly altered. Further in-depth investigation into the roles of cell subpopulations with significantly altered proportions in the onset and progression of IPF will provide valuable insights into the pathological mechanisms underlying the disease. This understanding could facilitate the development of novel therapeutic strategies and medications for IPF treatment.