星形胶质细胞通过缝隙连接对神经前体细胞分化的调控研究

Astrocytes play important role in regulating the differentiation fate of neural progenitor cells. Gap junction is critical to maintain the interaction inside neurons and astrocytes. However, the function of gap junction between neural progenitor cells or neurons and astrocytes are not defined. It had been proved that astrocytes could induce neurogenesis during differentiation of neural progenitor cells through two dimension cell-cell contact culture, while the underlying mechanism is still unclear. Therefore, we hypothesize that astrocytes could regulate neurongenesis of neural progenitor cells through gap junction, investigating the mechanism of how astrocytes regulate the neuron differentiation through three dimension cell-cell contact culture. Besides, the transcriptional regulation will be detected by RNA seq and eleven kinds of connexin that mainly expressed in central nervous system and formation of gap junction will be checked in neural progenitor cells during differentiation process. Our ultimate goal of this study is to reveal the underlying mechanism that how astrocytes regulate the differentiation of neural progenitor cells through the formation of gap junction ,which providing clues for the co-transplantation of neural progenitors cells and astrocytes in the future.

神经前体细胞的分化命运调控与星形胶质细胞有着密切的关系。细胞间缝隙连接在维持星形胶质细胞之间以及神经元之间的联系有着重要的作用，但对神经前体细胞和神经元与星形胶质细胞之间的缝隙连接功能仍缺乏研究。研究证明，星形胶质细胞可以通过二维接触式培养提高神经前体细胞向神经元分化的效率，但机制尚未明确。本项目以人同源的星形胶质细胞与神经前体细胞形成缝隙连接来诱导神经元的分化为假说，通过三维接触式共培养，探索神经元分化的效率和神经元功能的不同。同时用RNA高通量测序技术探究星形胶质细胞通过缝隙连接介导下的神经前体细胞分化过程中转录活动的变化，并检测神经前体细胞和神经元中11种神经系统特异缝隙蛋白（Cx）类型的表达与缝隙链接的形成。本项目拟揭示星形胶质细胞通过接触式作用对神经前体细胞缝隙连接的形成及其介导的神经元分化的机制，为提高神经前体细胞的神经元分化效率及进行神经前体细胞与星形胶质细胞共移植提供依据。