This research article utilized spatial transcriptomics to examine the complex cellular environments of idiopathic pulmonary fibrosis (IPF) in both human patients and mouse models. By mapping gene expression across lung tissues, the authors identified aberrant basaloid epithelial cells in humans and their counterparts in mice, providing new insights into how these cells drive irreversible scarring. The study highlights a critical difference in disease progression, showing that alveolar regeneration is successful in mice but becomes stalled or dysfunctional in human IPF. Researchers also uncovered significant roles for TGF-β and apolipoprotein signaling within the fibrotic niche, suggesting these pathways are key targets for future therapies. Ultimately, the findings emphasize the limitations of current preclinical models while offering a high-resolution atlas of the molecular interactions that prevent lung repair.

References:

• Franzén, L., Olsson Lindvall, M., Hühn, M. et al. Mapping spatially resolved transcriptomes in human and mouse pulmonary fibrosis. Nat Genet 56, 1725–1736 (2024). doi.org