Pathogenesis and Cells of Origin of Barrett's Esophagus

Jianwen Que, Katherine S. Garman, Rhonda F. Souza, Stuart Jon Spechler

Research output: Contribution to journalReview articlepeer-review

72 Scopus citations


In patients with Barrett's esophagus (BE), metaplastic columnar mucosa containing epithelial cells with gastric and intestinal features replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We review mechanisms of BE pathogenesis, including transdifferentiation and transcommitment, and discuss potential cells of origin, including basal cells of the squamous epithelium, cells of esophageal submucosal glands and their ducts, cells of the proximal stomach, and specialized populations of cells at the esophagogastric junction (residual embryonic cells and transitional basal cells). We discuss the concept of metaplasia as a wound-healing response, and how cardiac mucosa might be the precursor of the intestinal metaplasia of BE. Finally, we discuss shortcomings in current diagnostic criteria for BE that have important clinical implications.

Original languageEnglish (US)
Pages (from-to)349-364.e1
Issue number2
StatePublished - Aug 2019
Externally publishedYes


  • Esophageal Adenocarcinoma
  • Esophagogastric Junction
  • Gastroesophageal Reflux Disease
  • Metaplasia
  • Progenitor Cells

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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