Mapping cellular and ECM heterogeneity in pulmonary fibrosis—Insights from recent spatiomics studies

Idiopathic pulmonary fibrosis (IPF) features spatially heterogeneous tissue remodeling, with fibroblast foci (FF) acting as central hubs of fibrogenesis at the interface between remodeled and preserved alveolar regions. Emerging spatiomics studies reveal that FF comprise distinct functional zones-an activated fibroblast core, a transitional front, and surrounding mature fibrosis-each defined by unique cellular and molecular programs. Spatially resolved profiling has uncovered diverse fibroblast subpopulations, epithelial injury states, macrophage niches, and cell-matrix signaling circuits that together shape the fibrotic niche. By linking gene and protein expression to tissue architecture, spatiomics clarifies how fibroblast activation, epithelial remodeling, and ECM reorganization integrate across space to drive irreversible scarring. This Perspective summarizes spatiomics approaches in pulmonary fibrosis, synthesizes the key biological insights they have revealed, and highlights emerging opportunities-spanning integrative multiomics, AI-guided inference, and organoid models-to advance mechanistic understanding and therapeutic discovery in IPF.