SPT6 loss Permits the Transdifferentiation of Keratinocytes into an Intestinal Fate that Recapitulates Barrett’s Metaplasia
SPT6 loss Permits the Transdifferentiation of Keratinocytes into an Intestinal Fate that Recapitulates Barrett’s Metaplasia
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.
Vo Daniella T.、Fuller MacKenzie R.、Das Soumita、Sahoo Debashis、Anandachar Mahitha、Ghosh Pradipta、Tindle Courtney
Department of Pediatrics, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San Diego||HUMANOID Center of Research Excellence (CoRE), University of California San DiegoHUMANOID Center of Research Excellence (CoRE), University of California San Diego||Department of Pathology, University of California San Diego||Department of Computer Science and Engineering, Jacob?ˉs School of Engineering, University of California San DiegoDepartment of Pediatrics, University of California San Diego||Department of Computer Science and Engineering, Jacob?ˉs School of Engineering, University of California San Diego||Moore Comprehensive Cancer Center, University of California San DiegoDepartment of Pathology, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San Diego||HUMANOID Center of Research Excellence (CoRE), University of California San Diego||Department of Computer Science and Engineering, Jacob?ˉs School of Engineering, University of California San Diego||Moore Comprehensive Cancer Center, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San Diego||HUMANOID Center of Research Excellence (CoRE), University of California San Diego
基础医学分子生物学肿瘤学
Vo Daniella T.,Fuller MacKenzie R.,Das Soumita,Sahoo Debashis,Anandachar Mahitha,Ghosh Pradipta,Tindle Courtney.SPT6 loss Permits the Transdifferentiation of Keratinocytes into an Intestinal Fate that Recapitulates Barrett’s Metaplasia[EB/OL].(2025-03-28)[2025-07-16].https://www.biorxiv.org/content/10.1101/2021.05.06.442930.点此复制
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