Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus

Area of Science:

• Gastroenterology
• Stem Cell Biology
• Epithelial Biology

Background:

• Transitional zones between epithelia are prone to metaplasia and cancer.
• The cellular origins of Barrett's esophagus, a metaplastic change at the gastro-oesophageal junction, remain unclear.

Purpose of the Study:

• To identify the cell of origin for metaplasia in the gastro-oesophageal junction.
• To investigate the role of basal progenitor cells in the development of Barrett's esophagus.

Main Methods:

• Utilized mouse models and lineage tracing strategies.
• Examined the role of specific basal progenitor cells (p63+KRT5+KRT7+) at the squamous-columnar junction.
• Investigated the effect of CDX2 expression on progenitor cell differentiation.

Main Results:

• Identified a novel transitional columnar epithelium with distinct basal progenitor cells (p63+KRT5+KRT7+) at the upper gastrointestinal tract's squamous-columnar junction.
• Demonstrated that these basal progenitors give rise to the transitional epithelium.
• Showed that ectopic CDX2 expression induces differentiation into intestinal-like epithelium, mimicking Barrett's metaplasia.
• Observed similar transitional epithelium in other mouse tissues and the human gastro-oesophageal junction.
• Found expansion of these transitional basal progenitors in acid reflux-induced esophagitis and multilayered epithelium.

Conclusions:

• A previously unrecognized transitional zone and its basal progenitor cells (p63+KRT5+KRT7+) have been identified in the upper gastrointestinal tract.
• These basal cells are the source of progenitor cells for transitional epithelium and are the cells of origin for multilayered epithelium and Barrett's esophagus.