文章基本信息

标题：SPT6 loss permits the transdifferentiation of keratinocytes into an intestinal fate that resembles Barrett’s metaplasia
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作者：Daniella T. Vo ; MacKenzie R. Fuller ; Courtney Tindle 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：10
页码：1-17
DOI：10.1016/j.isci.2021.103121
语种：English
出版社：Elsevier
摘要：SummaryTransient 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 lend support to the notion that the keratinocytes are potentially the cell of origin of Barrett’s metaplasia but also provide mechanistic insights linking transient acid exposure, downregulation of SPT6, stalled transcription of the master regulator of epidermal fate TP63, loss of epidermal fate, and metaplastic progression. Because Barrett’s metaplasia in the esophagus 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.Graphical abstractDisplay OmittedHighlights•Keratinocytes transdifferentiate into a gut lineage upon depletion of SPT6•Such transdifferentiation resembles Barrett’s metaplasia not the healthy gut•Acid downregulates SPT6, which inhibits the expression and functions of TP63•Such downregulation precedes the metaplasia-dysplasia-neoplasia cascadeMolecular biology; Cell biology; Bioinformatics