ArticleDifferentiation; research in biological diversity
Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium.
Article in Differentiation; research in biological diversity. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Meta-Analysis Reveals the Prognostic Relevance of Nuclear and Membrane-Associated Bile Acid Receptors in Gastric Cancer.Clinical and translational gastroenterology · 2021Pooled it
- Single-cell atlas of cervical organoids uncovers epithelial immune heterogeneity and intercellular cross-talk during Chlamydia infection.Science advances · 2025Article
- Differential spatial distribution of HNF4α isoforms during dysplastic progression of intraductal papillary mucinous neoplasms of the pancreas.Scientific reports · 2023Article
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
- Expression profiling of CPS1 in Correa's cascade and its association with gastric cancer prognosis.Oncology letters · 2021Article
- GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells.Scientific reports · 2021Article
- Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment.Experimental & molecular medicine · 2021Review
- Review
- TGR5-HNF4α axis contributes to bile acid-induced gastric intestinal metaplasia markers expression.Cell death discovery · 2020Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
- The cyclical hit model: how paligenosis might establish the mutational landscape in Barrett's esophagus and esophageal adenocarcinoma.Current opinion in gastroenterology · 2019Review
- Identification of a primitive intestinal transcription factor network shared between esophageal adenocarcinoma and its precancerous precursor state.Genome research · 2019Article
- Origins of Metaplasia in Barrett's Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease?Digestive diseases and sciences · 2018Review
- Are Gastric and Esophageal Metaplasia Relatives? The Case for Barrett's Stemming from SPEM.Digestive diseases and sciences · 2018Review
- Oesophagus: A new candidate for the progenitor cell of Barrett metaplasia.Nature reviews. Gastroenterology & hepatology · 2018Article
- Cell fate conversion: a chromatin remodeling checkpoint revealed.Cell research · 2017Article
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype in adult mouse oesophageal epithelium and is present in the human condition. These data suggest that induction of HNF4α is a key early step in the formation of Barrett's metaplasia and are consistent with an origin of Barrett's metaplasia from the oesophageal epithelium.
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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.