Supplemental Material for: Fibroblast heterogeneity links inflammatory microenvironments to tissue remodeling in chronic rhinosinusitis

Fibroblasts contribute to extracellular matrix remodeling and immune regulation, but their heterogeneity in CRS remains unclear.</p><p dir="ltr"><b>Methods: </b>Public single-cell transcriptomic data from 21 CRS and healthy control samples were integrated with bulk RNA sequencing data from primary fibroblasts derived from nasal polyps stimulated with phosphate buffered saline (PBS), interferon (IFN)-γ, interleukin (IL)-4, or IL-17A.

Fibroblast subsets, pseudotime trajectories, and inferred communication between fibroblasts and immune cells were analyzed. Cytokine-induced signatures were projected onto the fibroblast atlas. A subset of longitudinal RNA-seq data from the COMPASS cohort (NCT05598424) was used to validate predefined candidate marker genes, including IL-4–associated markers of the C8 subset and IL-17A–associated markers of the C5/C10 subsets, during glucocorticoid treatment across V1 (baseline), V2 (after 4 weeks of intranasal corticosteroid treatment), and V3 (after subsequent systemic glucocorticoid therapy).