Single-Cell Sequencing Reveals Heterogeneity and Interactions Between Epithelial Cells and Fibroblasts in Post-ESD...

Oesophageal stricture, especially circumferential lesions, is a common complication of endoscopic submucosal dissection (ESD). However, the exact mechanisms underlying its development remain unclear. Consequently, understanding tissue microenvironment changes is crucial for identifying therapeutic targets. To address this, single-cell RNA sequencing (scRNA-seq) was performed on oesophageal stricture samples and normal controls. Alterations in cellular composition were observed, particularly in epithelial, endothelial, fibroblast and immune cells. A notable increase was observed in the number of differentiating suprabasal cell_2 (DFSC_2), which displayed pro-keratinizing traits. Detailed investigations revealed augmentation in a subset of these cells, characterised by elevated FTH1 and ECM1 expression, indicating their role in epithelial remodelling. Furthermore, fibroblast heterogeneity was demonstrated, with significant activation of myofibroblasts within stricture tissues. MDK-NCL, CXCL5/6-CXCR2, and TGFA-EGFR ligand-receptor pairs were enhanced in stricture tissues, mediating epithelial-stromal interactions. This study dissected the transcriptional landscape of postoperative oesophageal stricture tissues, providing valuable insights into stricture mechanisms and potential preventive strategies.