By generating a single-cell resolution spatial transcriptomic atlas of 127 fields from 43 patients, the study showed that a proliferative, dedifferentiated epithelial subpopulation drives ESCC progression by recruiting fibroblasts through JAG1–NOTCH1 signaling to form a protective CAF-epithelial niche at the tumor edge—an emergent microenvironmental hallmark that predicts disease advancement and patient outcomes. Here, JAG1 is linked to esophageal squamous cell carcinoma.