Modeling fibrotic alveolar transitional cells with pluripotent stem cell-derived alveolar organoids.

ABSTRACT: Repeated injury of the lung epithelium is proposed to be the main driver of idiopathic pulmonary fibrosis (IPF). However, available therapies do not specifically target the epithelium and human models of fibrotic epithelial damage with suitability for drug discovery are lacking. We developed a model of the aberrant epithelial reprogramming observed in IPF using alveolar organoids derived from human-induced pluripotent stem cells stimulated with a cocktail of pro-fibrotic and inflammatory cytokines. Deconvolution of RNA-seq data of alveolar organoids indicated that the fibrosis cocktail rapidly increased the proportion of transitional cell types including the KRT5 ^- /KRT17 ⁺ aberrant basaloid phenotype recently identified in the lungs of IPF

SUBMITTER: Ptasinski V 

PROVIDER: S-EPMC10213712 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature