P53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett's oesophagus.

ABSTRACT:

Background

While p53 mutations occur early in Barrett's oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear.

Objective

This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury.

Design

We used a BE mouse model (L2-IL1β) harbouring a Trp53 mutation (R172H) to study the effects of p53 on Cck2r⁺ cardia progenitor cells. We employed lineage tracing, pathological analysis, organoid cultures, single-cell RNA sequencing (scRNA-seq) and computational analyses to investigate changes in progenitor cell behaviour, differentiation patterns and tumour progression. Additionally,

SUBMITTER: Lian G 

PROVIDER: S-EPMC11741926 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature