Cellular Origins of Barrett’s Esophagus: the Search Continues

Purpose of Review: The cellular origins of Barrett’s esophagus remain elusive. In this review, we discuss the potential cellular mechanisms behind squamous to columnar metaplasia as well as the limitations of these proposed mechanisms. Recent Findings: Several theories have been proposed, including the reprogramming of native squamous cells, repopulation from submucosal glands, contributions from circulating bone marrow-derived cells, and direct extension of gastric cells. Most recent data support an innate progenitor cell unique to the squamocolumnar junction that can expand into metaplastic glands. Summary: Active investigation to clarify each of these potential cells of origin is being pursued, but ultimately each could contribute to the pathogenesis of Barrett’s esophagus depending on the clinical context. Nonetheless, identifying cells of origin is critical to understand the molecular mechanisms behind Barrett’s esophagus and developing strategies to better treat (and possibly prevent) this increasingly significant premalignant disease.