Integrated spatial and single-cell transcriptomics reveal PAK kinase as a therapeutic target in fibroblastic foci and dense fibrosis of idiopathic pulmonary fibrosis.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterised by progressive fibrosis of lung parenchyma. The histopathology of IPF exhibits temporal and spatial heterogeneity, including immature fibroblastic foci (FF) and densely collagenised fibrosis. FF serve as dynamic niches of pro-fibrotic fibroblasts and play a pivotal role in fibrosis progression and transition into dense fibrosis (DF). Here, we integrated single-cell RNA sequencing (scRNA-seq) with spatial transcriptomics to elucidate cellular heterogeneity and the novel cell type involved not only in FF formation, but also in DF development. We identified a novel myofibroblast population, WNT5A ⁺ CTHRC1 ⁺ myofibroblasts, enriched in both FF and DF regions, underscoring

SUBMITTER: Watanabe N 

PROVIDER: S-EPMC12501429 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature