TBX3介导YAP核质转运调控CTB细胞干性维持及分化参与FGR发生的机制研究

细胞滋养层细胞（CTB）的干性维持及分化是胎盘发育的基础，其功能异常可导致胎儿生长受限（FGR）的发生，但调控机制不明。本申请项目前期数据显示，TBX3与CTB细胞的干性维持及分化调控相关，其表达异常可能导致FGR的发生。基于前期的研究结果，本研究拟利用原代CTB细胞模型结合相关分子细胞技术探索：1）TBX3介导的YAP核质转运在CTB细胞干性维持及分化中的作用；2）TBX3调控YAP核质转运的机制及其对细胞周期的影响；3）TBX3介导的YAP核质转运与FGR发生的相关性，从而阐明本研究提出的“TBX3介导YAP核质转运参与调控CTB细胞的干性维持及分化”的机制假说。成果有望阐释CTB细胞干性维持及分化的调控机制和FGR的潜在病因。

The maintenance of stemness and differentiation of cytotrophoblast cells (CTB) is the basis of placental development. The abnormal function of CTB may lead to the occurrence of fetal growth restriction (FGR), but its regulatory mechanism is unclear. The preliminary data of this application project showed that TBX3 was involved in regulating CTB stemness maintenance and differentiation, and the abnormal expression of TBX3 may lead to the occurrence of FGR. Based on previous research, this study intends to use primary CTB model combined with related molecular cell technologies to explore: 1) The role of TBX3-mediated YAP nuclear-cytoplasmic translocation in the regulation of CTB stemness maintenance and differentiation; 2) The mechanism of TBX3-mediated YAP nuclear-cytoplasmic translocation and its effect on cell cycle; 3) the relationship between TBX3-mediated YAP nuclear-cytoplasmic translocation and FGR occurrence. Thus, the mechanism hypothesis of "TBX3-mediated YAP nuclear-cytoplasmic translocation is involved in regulating CTB stemness maintenance and differentiation" proposed in this study will be clarified. The results are expected to elucidate the mechanisms of CTB stemness maintenance and differentiation and the underlying etiology of FGR.