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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Hauptverfasser: Mattila, Jaakko (VerfasserIn) , Kokki, Krista (VerfasserIn) , Hietakangas, Ville (VerfasserIn) , Boutros, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 13, 2018
In: Developmental cell
Year: 2018, Jahrgang: 47, Heft: 1, Pages: 112-121, e1-e3
ISSN:1878-1551
DOI:10.1016/j.devcel.2018.08.011
Online-Zugang:Verlag, Volltext: https://doi.org/10.1016/j.devcel.2018.08.011
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1534580718306816
Volltext
Verfasserangaben:Jaakko Mattila, Krista Kokki, Ville Hietakangas, and Michael Boutros
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 17.10.2019
Beschreibung:Online Resource
ISSN:1878-1551
DOI:10.1016/j.devcel.2018.08.011