Back to Search Start Over

In vitro models of the human esophagus reveal ancestrally diverse response to injury

Authors :
Kateryna Karpoff
Jonathan Z. Sexton
Hogan Sp
Jiandie D. Lin
Daysha Ferrer-Torres
Emily M. Holloway
Caroline L. McCarthy
Spence
Joshua H. Wu
Angeline Wu
Hammer Ma
Margaret S Bohm
Yu-Hwai Tsai
Michael K. Dame
Shijiao Huang
Peter D.R. Higgins
Charles J. Zhang
D.K. Turgeon
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

SummaryEuropean Americans (EA) are more susceptible to esophageal tissue damage and inflammation when exposed to gastric acid and bile acid reflux and have a higher incidence of esophageal adenocarcinoma when compared to African Americans (AA). Population studies have implicated specific genes for these differences; however, the underlying cause for these differences is not well understood. We describe a robust long-term culture system to grow primary human esophagus in vitro, use single cell RNA sequencing to compare primary human biopsies to their in vitro counterparts, identify known and new molecular markers of basal cell types, and demonstrate that in vivo cellular heterogeneity is maintained in vitro. We further developed an ancestrally diverse biobank and a high-content, image based, screening assay to interrogate bile-acid injury response. These results demonstrated that AA esophageal cells responded significantly differently than EA-derived cells, mirroring clinical findings, having important implications for addressing disparities in early drug development pipelines.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........b13bd3a7bdbdb83d4f886cc8e9f1db3e