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Stem cell intrinsic hexosamine metabolism regulates intestinal adaptation to nutrient content

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 maint...

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Main Authors: Mattila, Jaakko (Author) , Kokki, Krista (Author) , Hietakangas, Ville (Author) , Boutros, Michael (Author)
Format: Article (Journal)
Language:English
Published: September 13, 2018
In: Developmental cell
Year: 2018, Volume: 47, Issue: 1, Pages: 112-121, e1-e3
ISSN:1878-1551
DOI:10.1016/j.devcel.2018.08.011
Online Access:Verlag, Volltext: https://doi.org/10.1016/j.devcel.2018.08.011
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1534580718306816
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Author Notes:Jaakko Mattila, Krista Kokki, Ville Hietakangas, and Michael Boutros

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520 |a 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 effect-like 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. 
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