人体细胞转化的胶质能NSCs在脑功能再生中的作用

项目名称： 人体细胞转化的胶质能NSCs在脑功能再生中的作用

项目编号： No.81200934

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 张炜

作者单位： 同济大学

项目金额： 23万元

中文摘要： 脑损伤已成为全世界主要健康与社会问题，合适的种子细胞（丰富来源、无致瘤性、无免疫排斥、无伦理限制、能重演神经发育过程）是实现脑功能再生的关键。转录因子诱导病人体细胞重编程来源的多能干细胞(iPSC)和神经元(iN)为脑损伤患者带来了治愈希望。但iPSCs存在致瘤性；iN是终末分化细胞，无能重现神经发育。文献报道胶质发生能神经干细胞(GNSC)可重演神经发育过程。基于此，本项目假设新重编程路径可将人体细胞转化为能重演神经发育过程的诱导型GNSC(iGNSC)。我们选择与NSC自我更新、增殖相关的转录因子进行不同组合，转化人成纤维细胞为iGNSC，将其移植裸大鼠脑损伤模型，从个体、细胞、分子三个层次分析其在脑功能再生中的作用。本课题以脑正常发育为基点，设计新重编程路径将体细胞转化为iGNSC，将完善体细胞重编程策略，为实现脑功能再生提供新手段和揭示再生机制提供新思路。

中文关键词： 胶质能神经干细胞；体细胞；脑损伤；示踪；神经环路

英文摘要： Brain injury has become the world's leading health and social problems. The seed cells (A rich source of non-tumorigenic, non-immune rejection, no ethical restrictions, representation of the process of neural development) are the key to the regeneration of brain function. Induced pluripotent stem cells (iPSC) and neurons (iN), which reprogrammed from somatic cells of patients by transcription factors, bring the hope of cure for patients with brain injury. But IPSCs may be tumorigenic, while iN is the terminally differentiated cells, can not reproduce the neurodevelopment. Literature reported glial occurrence of neural stem cells (GNSC) can repeat the process of neural development. Based on this literature, the project assume new reprogramming path can transform human body cells into inducible GNSC (iGNSC), which can repeat the process of neural development. We will choose transcription factor for NSC self-renewal, proliferation-related for different combinations, and transform human fibroblasts as iGNSC, then transplant it into brain injury model of nude mice, and analyze its role in the regeneration of brain function in three levels of the individual, cellular, molecular. The subject base on the normal development of brain, and design new reprogrammed path, transform body cells into iGNSC. The project was desig

英文关键词： glial occurrence of neural stem cells(GNSC)；body cells；brain injury；tracking；neural circuit