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- W4376641214 abstract "<div>Abstract<p>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.</p>Significance:<p>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.</p><p><i><a href=https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-23-0348 target=_blank>See related commentary by Stachler, p. 1291.</a></i></p><p><i><a href=https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-13-6-ITI target=_blank>This article is highlighted in the In This Issue feature, p. 1275</a></i></p></div>" @default.
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- W4376641214 date "2023-06-02" @default.
- W4376641214 modified "2023-10-18" @default.
- W4376641214 title "Data from Single-Cell RNA Sequencing Unifies Developmental Programs of Esophageal and Gastric Intestinal Metaplasia" @default.
- W4376641214 doi "https://doi.org/10.1158/2159-8290.c.6649141" @default.
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