Airway basal cells show a dedifferentiated KRT17^highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study, we focus on the properties of airway basal cells (ABC) obtained from patients with IPF (IPF-ABC). Single cell RNA sequencing (scRNAseq) of bronchial brushes revealed extensive reprogramming of IPF-ABC towards a KRT17^high PTEN^low dedifferentiated cell type. In the 3D organoid model, compared to ABC obtained from healthy volunteers, IPF-ABC give rise to more bronchospheres, de novo bronchial structures resembling lung developmental processes, induce fibroblast proliferation and extracellular matrix deposition in co-culture. Intratracheal application of IPF-ABC into minimally injured lungs of Rag2^-/- or NRG mice causes severe fibrosis, remodeling of the alveol

SUBMITTER: Jaeger B 

PROVIDER: S-EPMC9513076 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature