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Title: Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells

Abstract

We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation. In addition, mRNA levels of the stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) decreased in enteroids grown in Met deprivation conditions. Consistent with this observation, Met deprivation also attenuated Lgr5-EGFP fluorescence intensity in enteroids. In contrast, Met deprivation enhanced mRNA levels of the enteroendocrine cell marker chromogranin A (ChgA) and markers of K cells, enterochromaffin cells, goblet cells, and Paneth cells. Immunofluorescence experiments demonstrated that Met deprivation led to an increase in the number of ChgA-positive cells. These results suggest that Met deprivation suppresses stem cell proliferation, thereby promoting differentiation. In conclusion, Met is an important nutrient in the maintenance of intestinal stem cells and Met deprivation potentially affects cell differentiation. - Highlights: • Met influences the proliferation of enteroids.more » • Met plays a crucial role in the maintenance of stem cells. • Met deprivation potentially promotes differentiation into secretory cells.« less

Authors:
 [1];  [2]; ;  [1];  [3]; ;  [1];  [1]
  1. Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502 (Japan)
  2. Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502 (Japan)
  3. Department of Molecular and Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States)
Publication Date:
OSTI Identifier:
22697068
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 488; Journal Issue: 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL DIFFERENTIATION; CELL PROLIFERATION; CULTURE MEDIA; GOLGI COMPLEXES; METHIONINE; SMALL INTESTINE; STEM CELLS

Citation Formats

Saito, Yuki, Iwatsuki, Ken, Hanyu, Hikaru, Maruyama, Natsuki, Aihara, Eitaro, Tadaishi, Miki, Shimizu, Makoto, and Kobayashi-Hattori, Kazuo. Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.05.029.
Saito, Yuki, Iwatsuki, Ken, Hanyu, Hikaru, Maruyama, Natsuki, Aihara, Eitaro, Tadaishi, Miki, Shimizu, Makoto, & Kobayashi-Hattori, Kazuo. Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells. United States. doi:10.1016/J.BBRC.2017.05.029.
Saito, Yuki, Iwatsuki, Ken, Hanyu, Hikaru, Maruyama, Natsuki, Aihara, Eitaro, Tadaishi, Miki, Shimizu, Makoto, and Kobayashi-Hattori, Kazuo. Sat . "Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells". United States. doi:10.1016/J.BBRC.2017.05.029.
@article{osti_22697068,
title = {Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells},
author = {Saito, Yuki and Iwatsuki, Ken and Hanyu, Hikaru and Maruyama, Natsuki and Aihara, Eitaro and Tadaishi, Miki and Shimizu, Makoto and Kobayashi-Hattori, Kazuo},
abstractNote = {We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation. In addition, mRNA levels of the stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) decreased in enteroids grown in Met deprivation conditions. Consistent with this observation, Met deprivation also attenuated Lgr5-EGFP fluorescence intensity in enteroids. In contrast, Met deprivation enhanced mRNA levels of the enteroendocrine cell marker chromogranin A (ChgA) and markers of K cells, enterochromaffin cells, goblet cells, and Paneth cells. Immunofluorescence experiments demonstrated that Met deprivation led to an increase in the number of ChgA-positive cells. These results suggest that Met deprivation suppresses stem cell proliferation, thereby promoting differentiation. In conclusion, Met is an important nutrient in the maintenance of intestinal stem cells and Met deprivation potentially affects cell differentiation. - Highlights: • Met influences the proliferation of enteroids. • Met plays a crucial role in the maintenance of stem cells. • Met deprivation potentially promotes differentiation into secretory cells.},
doi = {10.1016/J.BBRC.2017.05.029},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 488,
place = {United States},
year = {2017},
month = {6}
}