果蝇肠道干细胞是具有制造肠道上皮细胞和肠道内分泌细胞两种子代细胞的多功能干细胞。最新研究表明，当肠道干细胞制造上皮细胞时，干细胞表达Notch信号通路的配体Dl，高水平激活上皮细胞中的Notch信号，促进上皮细胞分化；当干细胞制造内分泌细胞时，内分泌细胞表达Dl，低水平激活干细胞中的Notch信号，维持干细胞的特性。然而，Notch是如何在上皮细胞和干细胞中产生“高-低”两种不同的激活强度，并行使不同功能的？我们利用活体实时成像技术，惊奇的发现在干细胞制造内分泌细胞时，两个子代细胞采取“接触-离开”的运动模式；而当干细胞制造上皮细胞时，两个子代细胞始终处于紧密接触状态。因此我们大胆提出了干细胞与子代细胞间的互动模式决定“高-低”Notch信号强度的模型。我们申请通过进一步的细胞、分子、筛选、测序等实验验证我们提出的理论模型；深层次，多角度的解析干细胞多能分化的分子机理。

Drosophila intestinal stem cells (ISCs) generate enterocytes (ECs) and enteroendocrine (ee) cells. Latest work demonstrates that ISCs expressing Dl induce high Notch activity in daughter cells to promote EC formation during EC formation process. However, during ee cell formation, the ee daughter cell acts as a source of Dl that induces low Notch activity in the ISC to maintain stem cell identity. Obviously, as the Notch signaling only occurring between neighbor cells, the most intriguing question is how “High-Low” Notch signaling is achieved? By using live imaging technic, our unpublished data shows that the ee daughter and the ISC keep “touching and releasing” during ee cell formation; while the EC daughter and the ISC closely connect with each other during EC formation. Based on our observations, we suppose a model that the “High-Low” Notch signaling is depends on the dynamic of contact between two stem cell daughters. In order to better understand the molecular mechanism of multipotent stem cell differentiation, we are applying for this funding opportunity to support our next cellular, molecular, genetic, and sequencing experiments to further examine our model.