Author:
Franzén Lovisa,Lindvall Martina Olsson,Hühn Michael,Ptasinski Victoria,Setyo Laura,Keith Benjamin,Collin Astrid,Oag Steven,Volckaert Thomas,Borde Annika,Lundeberg Joakim,Lindgren Julia,Belfield Graham,Jackson Sonya,Ollerstam Anna,Stamou Marianna,Ståhl Patrik L,Hornberg Jorrit J
Abstract
AbstractIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. To address these limitations, we generated spatially resolved transcriptome maps of human IPF and bleomycin-induced mouse lung fibrosis. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by TGFβ signaling alongside factors such as p53 and ApoE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches, and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF.
Publisher
Cold Spring Harbor Laboratory
Reference72 articles.
1. Idiopathic pulmonary fibrosis
2. Spagnolo, P. et al. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development. Pharmacol Ther 222, 107798 (2021).
3. Mei, Q. , Liu, Z. , Zuo, H. , Yang, Z. & Qu, J . Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis. Front Pharmacol 12, 797292 (2021).
4. Adams, T.S. et al. Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis. Sci Adv 6, eaba1983 (2020).
5. Habermann, A.C. et al. Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci Adv 6, eaba1972 (2020).