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GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
Roman Stavniichuk1, Ann DeLaForest1, Cayla A Thompson1
1Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
Scientific Reports
|February 6, 2021
Summary
GATA4 drives columnar cell fate, potentially contributing to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Its expression in squamous cells represses squamous markers, suggesting a role in metaplasia.
Area of Science:
- Gastroenterology
- Molecular Biology
- Developmental Biology
Background:
- GATA4 promotes columnar epithelial cell fate.
- Ectopic GATA4 expression in mice mimics changes seen in Barrett's esophagus (BE).
- GATA4 is upregulated and amplified in BE and esophageal adenocarcinoma (EAC), correlating with poor outcomes.
Purpose of the Study:
- To investigate the effect of ectopic GATA4 expression in mature human esophageal squamous epithelial cells.
- To determine if GATA4 directly represses squamous cell marker genes.
- To assess GATA4 expression in BE and EAC and its induction by BE risk factors.
Main Methods:
- Ectopic GATA4 expression in human esophageal squamous epithelial cells.
- Analysis of squamous and columnar cell marker gene expression.
- Chromatin immunoprecipitation to assess GATA4 promoter occupancy.
- GATA4 protein and mRNA expression analysis in clinical samples and cell models.
Main Results:
- GATA4 expression in squamous cells reduced squamous marker genes and increased KRT8 (columnar marker).
- GATA4 occupied promoters of squamous cell marker genes (p63, KRT5, KRT15), suggesting direct repression.
- GATA4 protein was found in BE and EAC tissues.
- Acid and bile exposure induced GATA4 mRNA in esophageal squamous cells.
Conclusions:
- GATA4 suppresses genes characteristic of the stratified squamous epithelial lineage.
- GATA4's repressive action on squamous cell genes may play a role in the development of BE and EAC.
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