Clonal cell states link gastroesophageal junction tissues with metaplasia and cancer.

ABSTRACT: Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett's esophagus have not been resolved in humans. Here, we perform single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis unexpectedly reveals evidence for lineages spanning squamous esophagus, gastric cardia, and transitional basal cells at the tissue junction. We also identify lineages connecting Barrett's esophagus to both esophageal and gastric tissues. Barrett's esophagus biopsies consist of multiple distinct clones, with lineages that contain all progenitor and differentiated cell types. We discover Barre

SUBMITTER: Gier RA 

PROVIDER: S-EPMC12686426 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature