ROLE OF SOX9 IN CONTROLLING PANCREATIC PROGENITOR CELL PROPERTIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的实验室最近发现Sox9是一种专门标记胚胎胰腺干/祖细胞亚群的因子。在这个提案中，我将测试Sox9如何改变细胞的属性，以确保细胞保持祖细胞特征。通过比较正常的祖细胞和SOX9缺陷的祖细胞，我已经确定了细胞中哪些基因被Sox9激活。我发现，这些基因中的许多对于允许细胞与其他细胞进行特定连接，从而确保细胞之间的交流非常重要。利用小鼠体内特定时间的基因失活，我建议测试Sox9在多潜能胰腺祖细胞中的失活如何影响祖细胞产生β细胞的能力。然后，我将测试Sox9是否通过允许细胞与邻居进行适当的接触来控制β细胞的形成。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our lab has recently identified Sox9 as a factor that exclusively marks the stem/progenitor cell compartment in the embryonic pancreas. In this proposal, I will test how Sox9 alters the properties of a cell to ensure that the cell maintains progenitor cell characteristics. By comparing normal progenitors to Sox9-deficient progenitors, I have already determined which genes are activated by Sox9 in the cell. I found that many of these genes are important for allowing cells to make specific connections with other cells, thus ensuring communication between cells. Using time-specific gene inactivation in mice, I here propose to test how inactivation of Sox9 in multipotential pancreas progenitors affects the ability of progenitors to give rise to beta-cells. I will then test whether Sox9 controls beta-cell formation by allowing cells to make appropriate contacts with their neighbors.