2021
DOI: 10.1126/sciadv.abb2213
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Chemical conversion of human epidermal stem cells into intestinal goblet cells for modeling mucus-microbe interaction and therapy

Abstract: Intestinal goblet cells secrete mucus layers protecting the intestinal epithelia against injuries. It is challenging to study the interaction of goblet cells, mucus layers, and gut microbiota because of difficulty in producing goblet cells and mucus models. We generate intestinal goblet cells from human epidermal stem cells with two small molecular inhibitors Repsox and CHIR99021 in the presence of basic fibroblast growth factor and bone morphogenetic protein 4 at high efficiency (~95%) of conversion for a sho… Show more

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Cited by 17 publications
(12 citation statements)
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“…Several transcription factors, inflammatory cytokines and gut microbes have been implicated in the modulation of goblet cell differentiation. 38,39 ATOH1 (also called Math1), a Notch target gene, is involved in the differentiation of secretory lineages in the intestine. 40 Transcription factor SPDEF, previously thought to regulate goblet cell hyperplasia in the lung, was found to work downstream of ATOH1 to define differentiation toward secretory cell lineages, and its deficiency caused a severely impaired maturation of goblet and Paneth cells and an accumulation of immature secretory progenitors.…”
Section: Epa Promoted Mucin Production By Enhancing Goblet Cell Diffe...mentioning
confidence: 99%
“…Several transcription factors, inflammatory cytokines and gut microbes have been implicated in the modulation of goblet cell differentiation. 38,39 ATOH1 (also called Math1), a Notch target gene, is involved in the differentiation of secretory lineages in the intestine. 40 Transcription factor SPDEF, previously thought to regulate goblet cell hyperplasia in the lung, was found to work downstream of ATOH1 to define differentiation toward secretory cell lineages, and its deficiency caused a severely impaired maturation of goblet and Paneth cells and an accumulation of immature secretory progenitors.…”
Section: Epa Promoted Mucin Production By Enhancing Goblet Cell Diffe...mentioning
confidence: 99%
“…The observed changes in the number of mucus cells and activities of antioxidant enzymes in this study may have resulted from changes in intestinal microbiota that occurred under transport stress. Further studies using mucinous cell and goblet cell models would be useful to clarify the function of different types of mucinous cells and their changes under stress conditions [ 36 ].…”
Section: Discussionmentioning
confidence: 99%
“…The intestinal mucus layer is one crucial part of the gut barrier to preventing foreign invasion [16]. The mucins were synthesized, stored and secreted by goblet cells in the gut of animals [29]. When the mucus layer was defective, numerous bacteria could invade the host and cause serious immune response [17] and inflammatory bowel disease [30].…”
Section: Discussionmentioning
confidence: 99%