# Barrett's esophagus and progenitor cells at the squamous-columnar junction

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $356,000

## Abstract

SUMMARY
Columnar metaplasia, including Barrett’s esophagus (BE), is considered a precursor lesion of esophageal
adenocarcinoma which has seen a 600% fold increase in incidence over the last three decades. BE occurs
exclusively at the esophageal-gastro junction where the stratified squamous epithelium transitions into simple
columnar cells. In patients with BE the junction moves anteriorly and the columnar epithelium is expanded,
meanwhile gaining intestinal differentiation characteristics in some cases. Significantly, the cell-of-origin of the
metaplastic columnar epithelium remains controversial. Here, we identify a novel pseudostratified epithelium
maintained by a unique basal progenitor cell population (p63+, KRT5+, KRT7+) at the squamous-columnar
junction (SCJ). Our preliminary data suggest that the unique epithelium serves as the origin for BE metaplastic
epithelium in multiple mouse models. Our data further indicate that Wnt signaling promotes metaplastic changes
at the SCJ. We therefore hypothesize that columnar metaplasia including BE is derived from the unique basal
progenitor cells (p63+, KRT5+, KRT7+), a process promoted by Wnt signaling. We will test the hypothesis with
three specific aims: Aim 1: To further test that the basal progenitor cells (p63+, KRT5+, KRT7+) are the cells-
of-origin for columnar metaplasia including BE. Aim 2: To test the hypothesis that Wnt signaling promotes
columnar metaplasia at the SCJ and that inhibition of this signaling blocks disease progression. Aim 3: To model
the human BE pathogenic process with hESC-derived basal progenitor cells of the columnar epithelium. We
have established a robust in vitro system to induce the differentiation of human embryonic stem cells towards
basal cell fate. In this aim we will use this system to understand the mechanism driving the abnormal
differentiation of basal cells during BE development. Together findings from this project will contribute important
insights into early BE pathogenesis and provide potential therapeutic targets for treatment.

## Key facts

- **NIH application ID:** 9981728
- **Project number:** 5R01DK113144-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jianwen Que
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $356,000
- **Award type:** 5
- **Project period:** 2017-09-21 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981728

## Citation

> US National Institutes of Health, RePORTER application 9981728, Barrett's esophagus and progenitor cells at the squamous-columnar junction (5R01DK113144-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9981728. Licensed CC0.

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