Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Biochemistry

Background:

• Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by lung injury and excessive extracellular matrix (ECM) deposition.
• Understanding the specific cell types within fibrotic regions, such as fibroblast foci, is critical for deciphering IPF pathogenesis.

Purpose of the Study:

• To identify cell types associated with distinct histopathological regions in IPF lungs.
• To integrate spatial transcriptomics, single-cell RNA sequencing (scRNA-seq), and spatial proteomics for comprehensive analysis.
• To discover potential therapeutic targets for IPF intervention.

Main Methods:

• Integration of spatial transcriptomics and scRNA-seq data using Query and Overlap methods.
• Analysis of cell type enrichment in histopathological regions, including fibroblast foci.
• Application of laser capture microdissection-directed mass spectrometry for protein profiling.

Main Results:

• Distinct fibroblast populations are highly enriched in IPF fibroblast foci.
• Transitional alveolar type 2 and aberrant KRT5-/KRT17+ epithelial cells are associated with normal-appearing alveoli in IPF.
• Proteomic analysis identified ECM organization and collagen processing pathways in fibroblast foci.

Conclusions:

• Spatial multi-omics integration with scRNA-seq effectively identifies disease-associated cell types in IPF.
• The identified cell types and pathways provide potential targets for novel IPF therapies.
• This integrated approach is versatile and applicable to other spatially heterogeneous diseases.