Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content

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http://hdl.handle.net/10138/299365

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Mattila , J , Kokki , K , Hietakangas , V & Boutros , M 2018 , ' Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content ' , Developmental Cell , vol. 47 , no. 1 , pp. 112-+ . https://doi.org/10.1016/j.devcel.2018.08.011

Title: Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content
Author: Mattila, Jaakko; Kokki, Krista; Hietakangas, Ville; Boutros, Michael
Contributor: University of Helsinki, Centre of Excellence in Stem Cell Metabolism
University of Helsinki, Molecular and Integrative Biosciences Research Programme
Date: 2018-10-08
Language: eng
Number of pages: 13
Belongs to series: Developmental Cell
ISSN: 1534-5807
URI: http://hdl.handle.net/10138/299365
Abstract: The intestine is an organ with an exceptionally high rate of cell turnover, and perturbations in this process can lead to severe diseases such as cancer or intestinal atrophy. Nutrition has a profound impact on intestinal volume and cellular architecture. However, how intestinal homeostasis is maintained in fluctuating dietary conditions remains insufficiently understood. By utilizing the Drosophila midgut model, we reveal a novel stem cell intrinsic mechanism coupling cellular metabolism with stem cell extrinsic growth signal. Our results show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway (HBP) to monitor nutritional status. Elevated activity of HBP promotes Warburg effectlike metabolic reprogramming required for adjusting the ISC division rate according to nutrient content. Furthermore, HBP activity is an essential facilitator for insulin signaling-induced ISC proliferation. In conclusion, ISC intrinsic hexosamine synthesis regulates metabolic pathway activities and defines the stem cell responsiveness to niche-derived growth signals.
Subject: ADULT DROSOPHILA MIDGUT
INSULIN-RESISTANCE
WEIGHT CHANGE
GLUTAMINE
GROWTH
GLUCOSE
CANCER
PROLIFERATION
BIOSYNTHESIS
STARVATION
1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
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