American Association for Cancer Research
cd-22-0824_supplementary_table_s6_suppst6.xlsx (492.1 kB)

Supplementary Table S6 from Single-Cell RNA Sequencing Unifies Developmental Programs of Esophageal and Gastric Intestinal Metaplasia

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posted on 2023-05-16, 13:00 authored by Karol Nowicki-Osuch, Lizhe Zhuang, Tik Shing Cheung, Emily L. Black, Neus Masqué-Soler, Ginny Devonshire, Aisling M. Redmond, Adam Freeman, Massimilliano di Pietro, Nastazja Pilonis, Wladyslaw Januszewicz, Maria O'Donovan, Simon Tavaré, Jacqueline D. Shields, Rebecca C. Fitzgerald

This table contains marker genes identified in the pairwise comparison of clusters identified in fibroblast population



Intestinal metaplasia in the esophagus (Barrett's esophagus IM, or BE-IM) and stomach (GIM) are considered precursors for esophageal and gastric adenocarcinoma, respectively. We hypothesize that BE-IM and GIM follow parallel developmental trajectories in response to differing inflammatory insults. Here, we construct a single-cell RNA-sequencing atlas, supported by protein expression studies, of the entire gastrointestinal tract spanning physiologically normal and pathologic states including gastric metaplasia in the esophagus (E-GM), BE-IM, atrophic gastritis, and GIM. We demonstrate that BE-IM and GIM share molecular features, and individual cells simultaneously possess transcriptional properties of gastric and intestinal epithelia, suggesting phenotypic mosaicism. Transcriptionally E-GM resembles atrophic gastritis; genetically, it is clonal and has a lower mutational burden than BE-IM. Finally, we show that GIM and BE-IM acquire a protumorigenic, activated fibroblast microenvironment. These findings suggest that BE-IM and GIM can be considered molecularly similar entities in adjacent organs, opening the path for shared detection and treatment strategies. Our data capture the gradual molecular and phenotypic transition from a gastric to intestinal phenotype (IM) in the esophagus and stomach. Because BE-IM and GIM can predispose to cancer, this new understanding of a common developmental trajectory could pave the way for a more unified approach to detection and treatment.

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