Single-Cell RNA Sequencing Unifies Developmental Programs of Esophageal and Gastric Intestinal Metaplasia.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
02 06 2023
02 06 2023
Historique:
received:
27
07
2022
revised:
30
11
2022
accepted:
14
03
2023
medline:
5
6
2023
pubmed:
18
3
2023
entrez:
17
3
2023
Statut:
ppublish
Résumé
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. See related commentary by Stachler, p. 1291. This article is highlighted in the In This Issue feature, p. 1275.
Identifiants
pubmed: 36929873
pii: 718812
doi: 10.1158/2159-8290.CD-22-0824
pmc: PMC10236154
mid: EMS172799
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1346-1363Subventions
Organisme : Medical Research Council
ID : MR/W014122/1
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Organisme : Cancer Research UK
ID : G102382
Pays : United Kingdom
Organisme : Medical Research Council
ID : RG86932
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2023 The Authors; Published by the American Association for Cancer Research.
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