These results were verified in the single-cell transcriptomic data in hESCC samples from 60 patients (Fig. 3k and Supplementary Fig. 4g, h) and the bulk hESCC RNA sequencing data from 94 patients (Supplementary Fig. 4i, j) as reported previously.7,16 These results indicate that human esophageal cancer development has a similar molecular tissue segmentation to mESCC tumorigenic model and the aberrant EFNB1-EPHB4 interaction may play an important role in epithelial tissue oncogenic disorganization. Here, EPHB4 is linked to esophageal cancer.