Mapping spatially resolved transcriptomes in human and mouse pulmonary fibrosis.
Lovisa Franzén1,2, Martina Olsson Lindvall1, Michael Hühn3
1Safety Sciences, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
Nature Genetics
|July 1, 2024
Summary
Idiopathic pulmonary fibrosis (IPF) research reveals distinct fibrotic niches and aberrant cells. Targeting alveolar regeneration may offer a promising therapeutic strategy for this progressive lung disease.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Translational Research
Background:
- Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with limited treatment options.
- Understanding IPF pathogenesis and improving preclinical models are crucial for developing effective therapies.
Purpose of the Study:
- To generate spatially resolved transcriptome maps of human IPF and mouse pulmonary fibrosis models.
- To identify distinct fibrotic niches and cellular characteristics in IPF.
- To compare IPF with a preclinical model to understand disease mechanisms.
Main Methods:
- Spatially resolved transcriptome mapping of human IPF lung tissue (n=4).
- Spatially resolved transcriptome mapping of bleomycin-induced mouse pulmonary fibrosis (n=6).
- Comparative analysis of transcriptional landscapes between human IPF and mouse models.
Main Results:
- Distinct fibrotic niches identified in human IPF lungs.
- Aberrant alveolar epithelial cells and TGF-beta signaling dominate IPF niches.
- Arrested alveolar regeneration observed in IPF, contrasting with active repair in mouse models.
- TP53 and APOE identified as potential regulators in IPF fibrotic niches.
Conclusions:
- The study provides deep insights into the IPF transcriptional landscape.
- Alveolar regeneration emerges as a potential therapeutic strategy for IPF.
- Differences between human IPF and mouse models highlight challenges in preclinical translation.
