Abstract
Fibroblast heterogeneity remains undefined in eosinophilic esophagitis (EoE), an allergic inflammatory disorder complicated by fibrosis. We utilized publicly available single-cell RNA sequencing data (GSE201153) of EoE esophageal biopsies to identify fibroblast sub-populations, related transcriptomes, disease status-specific pathways and cell-cell interactions. IL13-treated fibroblast cultures were used to model active disease. At least 2 fibroblast populations were identified, F_A and F_B. Several genes including ACTA2 were more enriched in F_A. F_B percentage was greater than F_A and epithelial-mesenchymal transition upregulated in F_B vs. F_A in active and remission EoE. Epithelial-mesenchymal transition was also upregulated in F_B in active vs. remission EoE and TNF-α signaling via NFKB was downregulated in F_A. IL-13 treatment upregulated ECM-related genes more profoundly in ACTA2- fibroblasts than ACTA2+ myofibroblasts. After proliferating epithelial cells, F_B and F_A contributed most to cell-cell communication networks. ECM-Receptor interaction strength was stronger than secreted or cell-cell contact signaling in active vs. remission EoE and significant ligand-receptor pairs were driven mostly by F_B. This unbiased analysis identifies at least 2 fibroblast sub-populations in EoE in vivo, distinguished in part by ACTA2. Fibroblasts play a critical role in cell-cell interactions in EoE, most profoundly via ECM-receptor signaling via the F_B sub-group.