Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture

Abstract Adenomatous polyposis coli (APC) is a tumor-suppressing protein whose inactivation triggers the formation of colorectal polyps. Numerous studies using cell lines or genetically engineered mice have revealed its role in suppressing Wnt/β-catenin signaling pathway and regulating cell prolifer...

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Autores principales:	Daisuke Yamazaki, Osamu Hashizume, Shiho Taniguchi, Yosuke Funato, Hiroaki Miki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b1a581672fc4c0aa6e1d5883a21459d
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spelling	oai:doaj.org-article:2b1a581672fc4c0aa6e1d5883a21459d2021-12-02T14:03:46ZRole of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture10.1038/s41598-021-83590-62045-2322https://doaj.org/article/2b1a581672fc4c0aa6e1d5883a21459d2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83590-6https://doaj.org/toc/2045-2322Abstract Adenomatous polyposis coli (APC) is a tumor-suppressing protein whose inactivation triggers the formation of colorectal polyps. Numerous studies using cell lines or genetically engineered mice have revealed its role in suppressing Wnt/β-catenin signaling pathway and regulating cell proliferation and differentiation. Here, we performed genetic analyses of APC using a three-dimensional organoid culture of mouse colon epithelia, which enables the detailed examination of epithelial properties. Analyses of Apc-knockout colon organoids not only confirmed the importance of APC in suppressing Wnt/β-catenin signaling and regulating cell differentiation, but also revealed several novel features: a significant decrease in proliferating speed and an increase in cross-sectional area of cells. Moreover, we found a significant number of lysozyme-positive Paneth-like cells, which were never observed in wild-type colon tissues or organoids, but have been reported to emerge in colon cancers. Therefore, APC autonomously suppresses ectopic differentiation into lysozyme-positive cells, specifically in the colon epithelia. Colon organoids would be an ideal material to investigate the molecular mechanism and biological importance of the ectopic differentiation associated with cancer development.Daisuke YamazakiOsamu HashizumeShiho TaniguchiYosuke FunatoHiroaki MikiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daisuke Yamazaki Osamu Hashizume Shiho Taniguchi Yosuke Funato Hiroaki Miki Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture
description	Abstract Adenomatous polyposis coli (APC) is a tumor-suppressing protein whose inactivation triggers the formation of colorectal polyps. Numerous studies using cell lines or genetically engineered mice have revealed its role in suppressing Wnt/β-catenin signaling pathway and regulating cell proliferation and differentiation. Here, we performed genetic analyses of APC using a three-dimensional organoid culture of mouse colon epithelia, which enables the detailed examination of epithelial properties. Analyses of Apc-knockout colon organoids not only confirmed the importance of APC in suppressing Wnt/β-catenin signaling and regulating cell differentiation, but also revealed several novel features: a significant decrease in proliferating speed and an increase in cross-sectional area of cells. Moreover, we found a significant number of lysozyme-positive Paneth-like cells, which were never observed in wild-type colon tissues or organoids, but have been reported to emerge in colon cancers. Therefore, APC autonomously suppresses ectopic differentiation into lysozyme-positive cells, specifically in the colon epithelia. Colon organoids would be an ideal material to investigate the molecular mechanism and biological importance of the ectopic differentiation associated with cancer development.
format	article
author	Daisuke Yamazaki Osamu Hashizume Shiho Taniguchi Yosuke Funato Hiroaki Miki
author_facet	Daisuke Yamazaki Osamu Hashizume Shiho Taniguchi Yosuke Funato Hiroaki Miki
author_sort	Daisuke Yamazaki
title	Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture
title_short	Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture
title_full	Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture
title_fullStr	Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture
title_full_unstemmed	Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture
title_sort	role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2b1a581672fc4c0aa6e1d5883a21459d
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_version_	1718392069646450688

Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture

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