FUNCTIONAL ANALYSIS OF INTEGRATED WNT SIGNALS FOR SELF-RENEWAL OF THE HUMAN COLONIC EPITHELIUM

结肠的内层是由数百万个被称为隐窝的凹陷形成的。结肠内的大多数细胞每隔5天左右就会更新一次。干细胞在每个隐窝的底部不断产生未成熟的细胞后代，这些后代向上迁移。几天后，细胞到达隐窝表面并经历细胞死亡。为了维持结肠衬里的正常功能，细胞死亡率需要由细胞生成率来平衡。在隐窝中协调细胞产生和细胞死亡的机制尚不清楚。WNT信号最近被证明是维持上皮细胞的主要力量。然而，Wnt因子、特定信号和细胞过程的同一性尚不清楚。这项研究将利用一个完整的结肠上皮模型、最先进的生物成像技术和分子生物学的新组合，这些技术对于研究每个Wnt因子激活的细胞信号并确定对结肠上皮不断更新的后果是必要的。

The lining of the colon is formed by millions of invaginations called crypts. The majority of cells lining the colon are renewed every 5 days or so. Stem cells continuously produce immature cell offspring at the base of each crypt, which migrate upwards. After a few days the cells reach the crypt surface and undergo cell death. To sustain the normal function of the colon lining, the rate of cell death needs to be balanced by the rate of cell production. The mechanisms that coordinate cell production and cell death in the crypt are unknown. Wnt signals have recently been demonstrated to be a dominant force in the maintenance of the epithelium. However, the identity of the Wnt factors, specific signals and cellular processes are unknown. This study will utilise a novel combination of an intact model of the colon epithelium, state-of-the-art bioimaging techniques and molecular biology that are necessary to study the cellular signals activated by each Wnt factor and determine the consequences to the constant renewal of the colonic epithelium.