Sa124 GATA4 SUPPRESSES STRATIFIED SQUAMOUS CELL IDENTITY AND PROMOTES COLUMNAR CELL GENE EXPRESSION IN PATIENT-DERIVED ESOPHAGEAL EPITHELIAL CELLS

2021 ◽  
Vol 160 (6) ◽  
pp. S-429-S-430
Author(s):  
Olivia D. Franklin ◽  
Ann De La Forest ◽  
Roman Stavniichuk ◽  
Kirthi Pulakanti ◽  
Sridhar Rao ◽  
...  
2020 ◽  
Author(s):  
Roman Stavniichuk ◽  
Ann DeLaForest ◽  
Cayla A. Thompson ◽  
James Miller ◽  
Rhonda F. Souza ◽  
...  

ABSTRACTMetaplasia often involves a change from one cell type to another that was present during organogenesis. The embryonic esophagus is initially lined by columnar cells that are replaced by squamous cells, and metaplasia in Barrett’s esophagus (BE) involves a change from squamous to columnar cells in the setting of gastroesophageal reflux. Here, we explored the effect of ectopic expression of the essential developmental transcription factor GATA4 on squamous epithelial cell gene expression using human esophageal squamous epithelial cells. We found that GATA4 protein, although absent in mature human esophageal squamous epithelium, was present in BE and esophageal adenocarcinoma (EAC). Moreover, acid and bile induced GATA4 mRNA in esophageal squamous epithelial cells. Ectopic GATA4 expression in esophageal squamous epithelial cells generally compromised squamous cell marker gene expression, although the extent varied between cell lines studied. We observed GATA4 occupancy in the p63, KRT5, and KRT15 gene promoters, suggesting that GATA4 can directly repress expression of typical squamous epithelial cell marker genes. Overall, our data suggest a mechanism whereby GATA4 expression in abnormal esophageal cells, possibly induced by reflux, supports a columnar metaplastic cell identity by repressing expression of key genes required to program stratified squamous epithelial cell identity.


2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Idan Efroni ◽  
Pui-Leng Ip ◽  
Tal Nawy ◽  
Alison Mello ◽  
Kenneth D Birnbaum

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2313
Author(s):  
Suk-Ling Ma ◽  
Junyi Wu ◽  
Liuying Zhu ◽  
Ruth Chan ◽  
Amy Wang ◽  
...  

Background: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia. Methods: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone (n = 11), combined-exercise program and nutrition supplement (n = 23), and waitlist control group (n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests. Results: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups (p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes (RASGRP1, BIN1, LEF1, ANXA6, IL-7R, LRRN3, and PRKCQ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction. Conclusions: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.


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