Within a biopsy collected from a patient with high-grade dysplasia, we observed two large clusters of epithelial cells by scRNA-seq (Fig. 4a); one of the clusters consisted of cells that expressed established Barrett’s esophagus cell type markers, whereas the other did not, instead showing a marked loss of PIGR and FAM3D, known regulators of intestinal barrier integrity36,37 (Fig. S17). Here, FAM3D is linked to esophageal adenocarcinoma.