ArticleGastroenterology2021
Hybrid Stomach-Intestinal Chromatin States Underlie Human Barrett's Metaplasia.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- The mechanical niche in gastric precancer: extracellular matrix remodeling, mechanotransduction, and stem-cell fate.Frontiers in cell and developmental biology · 2026Review
- Metaplastic Barrett's oesophagus represents reversion to a developmental-like epithelial cell state.Development (Cambridge, England) · 2025Article
- Harnessing technologies to unravel gastric cancer heterogeneity.Trends in cancer · 2025Review
- Prognostic role of claudin-18.2 in intrahepatic cholangiocarcinoma.Virchows Archiv : an international journal of pathology · 2025Article
- Epigenomic heterogeneity as a source of tumour evolution.Nature reviews. Cancer · 2025Review
- Multi-Omics Meets Premalignancy: Paving the Way for Early Prevention of Cancer.Research (Washington, D.C.) · 2025Review
- Cellular Origins and Lineage Plasticity in Cancer.Cold Spring Harbor perspectives in medicine · 2024Review
- The pluripotency factor NANOG contributes to mesenchymal plasticity and is predictive for outcome in esophageal adenocarcinoma.Communications medicine · 2024Article
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- Review
- Genes Selectively Expressed in Rat Organs.Current genomics · 2024Article
- Article
- Targeting CLDN18.2 in cancers of the gastrointestinal tract: New drugs and new indications.Frontiers in oncology · 2023Review
- Shared features of metaplasia and the development of adenocarcinoma in the stomach and esophagus.Frontiers in cell and developmental biology · 2023Article
- COOBoostR: An Extreme Gradient Boosting-Based Tool for Robust Tissue or Cell-of-Origin Prediction of Tumors.Life (Basel, Switzerland) · 2022Article
- PredictiveNetwork: predictive gene network estimation with application to gastric cancer drug response-predictive network analysis.BMC bioinformatics · 2022Article
- A human Barrett's esophagus organoid system reveals epithelial-mesenchymal plasticity induced by acid and bile salts.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Impact of the Tumor Microenvironment for Esophageal Tumor Development-An Opportunity for Prevention?Cancers · 2022Review
- High-Resolution ATAC-Seq Analysis of Frozen Clinical Tissues.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsTissue metaplasia is uncommon in adults because established cis-element programs resist rewiring. In Barrett's esophagus, the distal esophageal mucosa acquires a predominantly intestinal character, with notable gastric features, and is predisposed to developing invasive cancers. We sought to understand the chromatin underpinnings of Barrett's metaplasia and why it commonly displays simultaneous gastric and intestinal properties.
methodsWe profiled cis-regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing. Mutations in Barrett's esophagus were examined in relation to tissue-specific enhancer landscapes using a random forest machine-learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett's biopsy specimens using the assay for transposase-accessible chromatin. We used 1- and 2-color immunohistochemistry to examine protein expression of tissue-restricted genes.
resultsBarrett's esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis-elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett's metaplasia coexpress gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins; CLDN18; and a novel gastric marker, ANXA10, showed extensive tissue and subclonal heterogeneity of dual stomach-intestinal cell states.
conclusionsThese findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett's esophagus. Pervasive intragland variation argues against stem-cell governance of this phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.