Cell子刊:肠道干细胞通过代谢调控来适应营养条件

创作:女巫 审核:小肠君 10月11日
在果蝇中肠模型中,肠道干细胞(ISC)利用氨基己糖生物合成途径(HBP)来监测并适应营养条件;
HBP调节ISC的丙酮酸代谢,HBP活性的升高促进ISC发生类似瓦氏效应的代谢重编程,使得ISC可根据营养含量调整分裂速率;
HBP与胰岛素信号通路互作,影响ISC增殖,HBP活性是促进胰岛素信号诱导的ISC增殖的重要因子;
ISC固有的氨基己糖合成过程可调节代谢通路的活性,并决定了ISC对来自生境的特定生长信号的反应。
延伸阅读
Developmental Cell [IF:9.616]

Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content

干细胞固有的氨基己糖代谢可调节肠道对营养条件的适应性

09-07, Article, 10.1016/j.devcel.2018.08.011more

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.

First Authors:
Jaakko Mattila

Correspondence Authors:
Michael Boutros

All Authors:
Jaakko Mattila,Krista Kokki,Ville Hietakangas,Michael Boutros