SUMMARY
Transient depletion of the transcription elongation factor SPT6 in the keratinocyte has been recently shown to inhibit epidermal differentiation and stratification; instead, they transdifferentiate into a gut-like lineage. We show here that this phenomenon of transdifferentiation recapitulates Barrett’s metaplasia, the only human pathophysiologic condition in which a stratified squamous epithelium that is injured due to chronic acid reflux is trans-committed into an intestinal fate. The evidence we present here not only pinpoint the keratinocyte as the cell of origin of Barrett’s metaplasia, but also provide mechanistic insights linking chronic acid injury, downregulation of SPT6, loss of epidermal fate and metaplastic progression. Because Barrett’s metaplasia in the esophagus (BE) is a pre-neoplastic condition with no preclinical human models, these findings have a profound impact on the modeling Barrett’s metaplasia-in-a-dish.
Competing Interest Statement
The authors have declared no competing interest.