Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content

Developmental Cell
Jaakko MattilaMichael Boutros

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 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.

Citations

Sep 7, 2019·G3 : Genes - Genomes - Genetics·Dona R Wisidagama, Carl S Thummel
Jun 23, 2020·EMBO Reports·Maja C FunkMichael Boutros
Jul 31, 2019·Cell and Tissue Research·Silvia CacciaGianluca Tettamanti
Feb 9, 2021·Trends in Cell Biology·Siamak Redhai, Michael Boutros
Mar 6, 2021·Cell Stem Cell·Cesar A Perez-Ramirez, Heather R Christofk

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Datasets Mentioned

BETA
GSE107052

Methods Mentioned

BETA
glycosylation
RNAseq

Software Mentioned

Bioconductor package piano
R
ImageJ
limma
Bioconductor
Trimmomatic
runGSA
FASTQC

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