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Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice

The activity of intestinal stem cells (ISCs) is foremost in maintaining homeostasis and repair of intestines. As a pivotal substrate of RNA and DNA biosynthesis, uridine plays essential roles in nutritional and disease monitoring. Whether uridine influences ISC activity remains undefined. To answer...

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Autores principales: Liu, Yi-Lin, Guo, Song-Ge, Xie, Chun-yan, Niu, Kaimin, De Jonge, Hugo, Wu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049648/
https://www.ncbi.nlm.nih.gov/pubmed/35496025
http://dx.doi.org/10.1039/c9ra07742a
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author Liu, Yi-Lin
Guo, Song-Ge
Xie, Chun-yan
Niu, Kaimin
De Jonge, Hugo
Wu, Xin
author_facet Liu, Yi-Lin
Guo, Song-Ge
Xie, Chun-yan
Niu, Kaimin
De Jonge, Hugo
Wu, Xin
author_sort Liu, Yi-Lin
collection PubMed
description The activity of intestinal stem cells (ISCs) is foremost in maintaining homeostasis and repair of intestines. As a pivotal substrate of RNA and DNA biosynthesis, uridine plays essential roles in nutritional and disease monitoring. Whether uridine influences ISC activity remains undefined. To answer this question, 3-dimensional (3D) mouse intestinal organoids and living mice were used as a model. It was found that uridine causes a significant decrease in the number of crypts per intestinal organoid. Uridine also significantly decreases mRNA expression and protein levels with markers of ISCs in intestinal organoids in a dose-dependent manner, which was instructed via mTOR. In parallel, uridine decreases the expression of marker of ISCs in mouse intestine in vivo. Our findings are the first to demonstrate that uridine is able to govern the functions of ISCs in intestinal organoid and mouse models. Thus, this study may provide a useful reference for developing novel functional food bioactives that maintain intestinal homeostasis.
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spelling pubmed-90496482022-04-29 Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice Liu, Yi-Lin Guo, Song-Ge Xie, Chun-yan Niu, Kaimin De Jonge, Hugo Wu, Xin RSC Adv Chemistry The activity of intestinal stem cells (ISCs) is foremost in maintaining homeostasis and repair of intestines. As a pivotal substrate of RNA and DNA biosynthesis, uridine plays essential roles in nutritional and disease monitoring. Whether uridine influences ISC activity remains undefined. To answer this question, 3-dimensional (3D) mouse intestinal organoids and living mice were used as a model. It was found that uridine causes a significant decrease in the number of crypts per intestinal organoid. Uridine also significantly decreases mRNA expression and protein levels with markers of ISCs in intestinal organoids in a dose-dependent manner, which was instructed via mTOR. In parallel, uridine decreases the expression of marker of ISCs in mouse intestine in vivo. Our findings are the first to demonstrate that uridine is able to govern the functions of ISCs in intestinal organoid and mouse models. Thus, this study may provide a useful reference for developing novel functional food bioactives that maintain intestinal homeostasis. The Royal Society of Chemistry 2020-02-11 /pmc/articles/PMC9049648/ /pubmed/35496025 http://dx.doi.org/10.1039/c9ra07742a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Liu, Yi-Lin
Guo, Song-Ge
Xie, Chun-yan
Niu, Kaimin
De Jonge, Hugo
Wu, Xin
Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice
title Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice
title_full Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice
title_fullStr Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice
title_full_unstemmed Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice
title_short Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice
title_sort uridine inhibits the stemness of intestinal stem cells in 3d intestinal organoids and mice
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049648/
https://www.ncbi.nlm.nih.gov/pubmed/35496025
http://dx.doi.org/10.1039/c9ra07742a
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