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Ex vivo lung-organoid model for aberrant basaloid cell induction and activation

ABSTRACT: Lung epithelial cell injury contributes to various lung diseases, impacting lung function and overall human health. Bleomycin (BLM)-induced murine models of pulmonary fibrosis (PF) are commonly utilized to study lung epithelial cell injury. However, the complex microenvironments in inflamed lungs hinder clear causal relationships between cell-to-cell, molecules interaction. To address this limitation, we aimed to establish an ex vivo organoid model of BLM-induced lung injury recapitulating the cellular and molecular responses of BLM-induced lung epithelial injury in vivo.

ORGANISM(S): Mus musculus

PROVIDER: GSE249285 | GEO | 2025/11/04

REPOSITORIES: GEO

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TIme-cource single-cell RNA-seq analysis of bleomycin and LPS-induced lung injury and fibrosis

Project description:Pulmonary fibrosis (PF) is a progressive fibrotic disease with a poor prognosis and suboptimal therapeutic options. To construct comprehensive single-cell atlas and identify disease-relevant cell subsets and gene signatures of the murine models of PF pathogenesis and lung repair, time-course singel-cell RNA-seq analysis of bleomycin (BLM) and LPS-induced lung injury/fibrosis models were performed. We sampled mouse lungs of untreated, day3, 7, 14, 28, 42, 63 (BLM model, 1.25 mg/kg), day3, 7, 14 (3 mg/kg), and day7, 14, 42 (LPS model, 1mg/ml, 50ul/head) with 5 biological replicates (except BLM 3mg/kg at day 14 which includes 2 biological replicate) and processed by using TAS-Seq protocol (Shichino et al. Commnue Biol 2022). We found that some of the early phase-specific markers, and repair phase-specific cell subsets and associated gene signatures. Of these, we found that Sftpb was an early marker of lung injury that was specifically expressed on AT2 cells, and SFTPC protein also highly expressed in the serum extracellular vesicles from prognosis-worsen PF-ILD patients. Our dataset might useful to clarify lung injury and repair mechanisms.

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