biostudies-literatureUnknownGier RANCATS NIH HHSNIDDK NIH HHSNIH HHSBarrett'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. To address this, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis revealed discrete lineages in Barrett's esophagus, normal esophagus, and gastric cardia. Transitional basal progenitor cells of the gastroesophageal junction were unexpectedly related to both esophagus and gastric cardia cells. Barrett's esophagus was polyclonal, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic foci were initiated by the expansion of a single molecularly aberrant Barrett's esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the full disease trajectory, from its origin to cancer.bioRxiv : the preprint server for biology2023.01.26.525564https://www.ebi.ac.uk/biostudies/studies/S-EPMC9900873biostudies-literatureClonal cell states link Barrett's esophagus and esophageal adenocarcinoma.PMC9900873DP5 OD028144P30 DK050306R01 DK124266UL1 TR001878Muir ABHueros RARGier RAKarakasheva TAFalk GWRong JZhang NRShaffer SMDeMarshall MfalseClonal cell states link Barrett's esophagus and esophageal adenocarcinoma.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. To address this, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis revealed discrete lineages in Barrett's esophagus, normal esophagus, and gastric cardia. Transitional basal progenitor cells of the gastroesophageal junction were unexpectedly related to both esophagus and gastric cardia cells. Barrett's esophagus was polyclonal, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic foci were initiated by the expansion of a single molecularly aberrant Barrett's esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the full disease trajectory, from its origin to cancer.2023-01-01T00:00:00Z2023 Feb2025-04-19T13:32:57.358Z2025-04-19T13:32:57.358ZS-EPMC99008733674770810.1101/2023.01.26.525564