The Cellular Origin of Barrett’s Esophagus and Its Stem Cells

Wa Xian, Marcin Duleba, Yanting Zhang, Yusuke Yamamoto, Khek Yu Ho, Christopher Crum, Frank McKeon

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations


The incidence of esophageal adenocarcinoma is rapidly increasing in Western countries. This is despite the introduction of sophisticated endoscopic techniques and our ability to readily monitor the presumed precursor lesion known as Barrett’s esophagus. Preemptive approaches, including radiofrequency ablation (RFA), and photodynamic therapy (PDT) for Barrett’s esophagus and dysplasia are achieving dramatic initial results. Although the long-term efficacy of these nonspecific ablative therapies is awaiting longitudinal studies, reports of recurrences are increasing. More targeted therapies, particularly directed at the stem cells of Barrett’s esophagus, demand knowing the origin of this intestinal metaplasia (IM). The prevailing concept holds that Barrett’s esophagus arises from the “transcommitment” of esophageal stem cells to produce an intestine-like epithelium. An alternative explanation derives from the discovery of a discrete population of residual embryonic cells (RECs) existing at the gastroesophageal junction in normal individuals that expands and colonizes regions of the esophagus denuded by chronic reflux. These RECs form IM within days of esophageal injury, suggesting a novel mechanism of tumorigenesis. A corollary of this work is that the Barrett’s stem cell is distinct from that of the squamous epithelium and, once identified, will form the basis of new preemptive strategies for addressing Barrett’s and its related neoplasia.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Number of pages15
StatePublished - 2019
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • Adult stem cells
  • Barrett’s esophagus
  • Cancer precursor
  • Cancer prevention
  • Esophageal adenocarcinoma
  • High-throughput screening
  • Intestinal metaplasia
  • Preemptive therapeutics
  • Residual embryonic cells
  • Stem cell cloning

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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