神经干细胞具有重要的基础研究和临床应用价值，我们前期研究发现小分子化合物组合可以诱导小鼠成纤维细胞转分化为神经干细胞，并且该诱导过程中伴随着核孔蛋白Nup210的阶段性激活以及关键转录因子Sox2的表达。基于此，我们推测小分子化合物组合通过Nup210激活Sox2表达并维持二者相互作用，从而诱导神经干细胞产生。但对于Nup210如何调控Sox2的表达，二者之间如何相互作用的机制与意义尚不清楚。因此，本课题将对如下科学问题进行研究：1、Nup210如何调控Sox2表达，从而促进细胞转分化的产生？2、Nup210是否与Sox2相互作用维持诱导产生的神经干细胞的生物学功能？3、基于以上研究，能否获得新的小分子化合物组合，从而进一步提高细胞转分化的诱导效率？该研究结果将不但阐明小分子化合物组合诱导小鼠体细胞转分化为神经干细胞的分子机制，而且为其他小分子化合物组合调控细胞命运转变的研究提供了借鉴。

Neural stem cells (NSCs) are valuable for both basic research and clinical application. We found that cocktail of small molecule compounds could convert mouse fibroblasts into NSCs, which were named as chemical-induced NSCs (ciNSCs). We also found that the converting process was accompanied by stepwise activation of nucleoporin Nup210 and Sox2. Based on these findings, we speculate that the chemical cocktail activates Sox2 expression is through Nup210 at early time and maintains the interaction between them later, which leads to ciNSC generation. However, the mechanism underling Nup210 regulating Sox2 or Nup210 interacting with Sox2 remains unknown. In this study, we are going to focus on three key questions: 1. How does Nup210 regulate Sox2 then help converting mouse fibroblasts into ciNSCs? 2. Whether Nup210 interacts with Sox2 to maintain ciNSC function? 3. Is it possible to convert mouse fibroblasts into ciNSCs at higher efficiency with new chemical cocktail in comparison with previous one, based on uncovering the proposed molecular mechanism? This study will not only help us understating the molecular mechanism of cell conversion from mouse fibroblasts into NSCs by chemical cocktail, but also shed light on the elucidation of the mechanism of other functional cell generation via chemical induced cell fate change.