微小RNA miR-305对胰岛素和Notch信号通路活性的协调作用介导了果蝇肠道干细胞中的适应性稳态。

Coordination of insulin and Notch pathway activities by microRNA miR-305 mediates adaptive homeostasis in the intestinal stem cells of the Drosophila gut.

作者信息

Foronda David, Weng Ruifen, Verma Pushpa, Chen Ya-Wen, Cohen Stephen M

机构信息

Institute of Molecular and Cell Biology, Singapore 138673, Singapore;

Institute of Molecular and Cell Biology, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore

出版信息

Genes Dev. 2014 Nov 1;28(21):2421-31. doi: 10.1101/gad.241588.114.

DOI:10.1101/gad.241588.114

PMID:25367037

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4215186/

Abstract

Homeostasis of the intestine is maintained by dynamic regulation of a pool of intestinal stem cells. The balance between stem cell self-renewal and differentiation is regulated by the Notch and insulin signaling pathways. Dependence on the insulin pathway places the stem cell pool under nutritional control, allowing gut homeostasis to adapt to environmental conditions. Here we present evidence that miR-305 is required for adaptive homeostasis of the gut. miR-305 regulates the Notch and insulin pathways in the intestinal stem cells. Notably, miR-305 expression in the stem cells is itself under nutritional control via the insulin pathway. This link places regulation of Notch pathway activity under nutritional control. These findings provide a mechanism through which the insulin pathway controls the balance between stem cell self-renewal and differentiation that is required for adaptive homeostasis in the gut in response to changing environmental conditions.

摘要

肠道的稳态是通过对肠道干细胞库的动态调节来维持的。干细胞自我更新与分化之间的平衡由Notch和胰岛素信号通路调节。对胰岛素通路的依赖使干细胞库处于营养控制之下，从而使肠道稳态能够适应环境条件。在此，我们提供证据表明miR-305是肠道适应性稳态所必需的。miR-305在肠道干细胞中调节Notch和胰岛素通路。值得注意的是，干细胞中miR-305的表达本身通过胰岛素通路受营养控制。这种联系使Notch通路活性的调节处于营养控制之下。这些发现提供了一种机制，通过该机制胰岛素通路控制肠道适应性稳态中干细胞自我更新与分化之间的平衡，以应对不断变化的环境条件。