Signaling in the crypt: a novel metabolic pathway in intestinal stem cells

肠道是体内更新最快的组织，由高度活跃的干细胞利基驱动。胆汁酸正在成为干细胞生态位的关键调节者，胆汁酸稳态的破坏会对肠道更新产生深远的不利影响，从而影响肠道健康。我们正在解决我们在理解如何在干细胞利基内控制胆汁酸方面的一个关键差距。该项目的目的是确定一种名为UGT8的新型酶在控制肠道干细胞对胆汁酸的反应中的关键作用；这是通过调节肠道干细胞模型中的UGT8活性并确定对干细胞功能的影响以及控制肠道内稳态和更新的关键信号通路来实现的。

The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.