Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging

Epigenetic silencing of Lgr5 in aged organoids To understand the molecular features underlying stem cell aging, we established intestinal epithelial organoids derived from both young and aged mice, and investigated alterations in their senescence and epigenetic status. Senescence-related changes inc...

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Autores principales:	Ryoei Uchida, Yoshimasa Saito, Kazuki Nogami, Yohei Kajiyama, Yukana Suzuki, Yasuhiro Kawase, Toshiaki Nakaoka, Toshihide Muramatsu, Masaki Kimura, Hidetsugu Saito
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/e1c53da2776440f3a69b4e2f9cf4edf3
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spelling	oai:doaj.org-article:e1c53da2776440f3a69b4e2f9cf4edf32021-12-02T14:22:33ZEpigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging10.1038/s41514-018-0031-52056-3973https://doaj.org/article/e1c53da2776440f3a69b4e2f9cf4edf32018-12-01T00:00:00Zhttps://doi.org/10.1038/s41514-018-0031-5https://doaj.org/toc/2056-3973Epigenetic silencing of Lgr5 in aged organoids To understand the molecular features underlying stem cell aging, we established intestinal epithelial organoids derived from both young and aged mice, and investigated alterations in their senescence and epigenetic status. Senescence-related changes including accumulation of senescence-associated β-galactosidase were observed in intestinal epithelial organoids derived from aged mice. We also demonstrated that the important stem cell marker Lgr5 was epigenetically silenced by trimethylation of histone H3 lysine 27, inducing suppression of Wnt signaling and a decrease of cell proliferation in organoids from aged mice. Our results suggest that organoids derived from aged animals could be a powerful research tool for investigating the molecular mechanisms underlying stem cell aging and for development of some form of anti-aging intervention, thus contributing to prolongation of healthy life expectancy.Ryoei UchidaYoshimasa SaitoKazuki NogamiYohei KajiyamaYukana SuzukiYasuhiro KawaseToshiaki NakaokaToshihide MuramatsuMasaki KimuraHidetsugu SaitoNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 4, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Ryoei Uchida Yoshimasa Saito Kazuki Nogami Yohei Kajiyama Yukana Suzuki Yasuhiro Kawase Toshiaki Nakaoka Toshihide Muramatsu Masaki Kimura Hidetsugu Saito Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging
description	Epigenetic silencing of Lgr5 in aged organoids To understand the molecular features underlying stem cell aging, we established intestinal epithelial organoids derived from both young and aged mice, and investigated alterations in their senescence and epigenetic status. Senescence-related changes including accumulation of senescence-associated β-galactosidase were observed in intestinal epithelial organoids derived from aged mice. We also demonstrated that the important stem cell marker Lgr5 was epigenetically silenced by trimethylation of histone H3 lysine 27, inducing suppression of Wnt signaling and a decrease of cell proliferation in organoids from aged mice. Our results suggest that organoids derived from aged animals could be a powerful research tool for investigating the molecular mechanisms underlying stem cell aging and for development of some form of anti-aging intervention, thus contributing to prolongation of healthy life expectancy.
format	article
author	Ryoei Uchida Yoshimasa Saito Kazuki Nogami Yohei Kajiyama Yukana Suzuki Yasuhiro Kawase Toshiaki Nakaoka Toshihide Muramatsu Masaki Kimura Hidetsugu Saito
author_facet	Ryoei Uchida Yoshimasa Saito Kazuki Nogami Yohei Kajiyama Yukana Suzuki Yasuhiro Kawase Toshiaki Nakaoka Toshihide Muramatsu Masaki Kimura Hidetsugu Saito
author_sort	Ryoei Uchida
title	Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging
title_short	Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging
title_full	Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging
title_fullStr	Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging
title_full_unstemmed	Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging
title_sort	epigenetic silencing of lgr5 induces senescence of intestinal epithelial organoids during the process of aging
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e1c53da2776440f3a69b4e2f9cf4edf3
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Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging

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