Li Tao, Salomon Matthew, Shao Ling, Khalatbari Atousa, Castle Joshua D, Shaker Anisa
Swallowing and Esophageal Disorders Center, Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA 90089, USA.
Research Center for Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90089, USA.
Biology (Basel). 2024 Jun 21;13(7):461. doi: 10.3390/biology13070461.
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 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 . Fibroblasts play a critical role in cell-cell interactions in EoE, most profoundly via ECM-receptor signaling via the F_B sub-group.
在嗜酸性粒细胞性食管炎（EoE）中，成纤维细胞异质性仍未明确，这是一种伴有纤维化的过敏性炎症性疾病。我们利用公开可用的EoE食管活检单细胞RNA测序数据（GSE201153）来识别成纤维细胞亚群、相关转录组、疾病状态特异性途径和细胞间相互作用。用白细胞介素13（IL13）处理的成纤维细胞培养物用于模拟活动性疾病。至少鉴定出2个成纤维细胞群体，F_A和F_B。包括 在内的几个基因在F_A中更富集。F_B的百分比大于F_A，并且在活动性和缓解期EoE中，F_B相对于F_A的上皮-间质转化上调。在活动性与缓解期EoE中，F_B中的上皮-间质转化也上调，并且F_A中通过核因子κB（NFKB）的肿瘤坏死因子-α（TNF-α）信号传导下调。与α-平滑肌肌动蛋白（ACTA2）阳性的肌成纤维细胞相比，IL-13处理在ACTA2阴性的成纤维细胞中更显著地上调细胞外基质（ECM）相关基因。在增殖上皮细胞后，F_B和F_A对细胞间通讯网络的贡献最大。在活动性与缓解期EoE中，ECM-受体相互作用强度强于分泌或细胞间接触信号传导，并且重要的配体-受体对主要由F_B驱动。这种无偏分析在体内EoE中鉴定出至少2个成纤维细胞亚群，部分区别在于 。成纤维细胞在EoE的细胞间相互作用中起关键作用，最主要是通过F_B亚组的ECM-受体信号传导。
