A Robust Single Primate Neuroepithelial Cell Clonal Expansion System for Neural Tube Development and Disease Studies
A Robust Single Primate Neuroepithelial Cell Clonal Expansion System for Neural Tube Development and Disease Studies
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DOI：
10.1016/j.stemcr.2015.10.007
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发表时间：
2015-11
影响因子：
5.9
通讯作者：
Xiaoqin Zhu;Bo Li;Zongyong Ai;Zheng Xiang;Kunshan Zhang;Xiaoyan Qiu;Yongchang Chen;Yuemin Li
中科院分区：
文献类型：
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作者：
Xiaoqin Zhu;Bo Li;Zongyong Ai;Zheng Xiang;Kunshan Zhang;Xiaoyan Qiu;Yongchang Chen;Yuemin Li
建立灵长类神经管发育模型对促进模式生物神经管紊乱的研究具有重要意义。在这里，我们报告了一个强大和稳定的系统，允许克隆扩增单个猴子神经上皮干细胞（NESCs）发育成微型nt样结构。单个NESCs可以在体外产生功能神经元，存活，并在猴脑内广泛再生神经元轴突。NT的形成和NESC的维持依赖于高代谢活性和Wnt信号。NESCs局部局限于端脑的命运。此外，单个NESCs可以转化为放射状胶质祖细胞（RGPCs）。这种转变是由Wnt信号通过Notch信号和粘附分子的调控精确调控的。最后，利用“NESC-TO-NTs”系统，我们模拟了叶酸（FA）对NT关闭的功能，并证明了FA可以调节多种机制来预防NT缺陷。我们的系统是研究NT发展和疾病的理想选择。
Developing a model of primate neural tube (NT) development is important to promote many NT disorder studies in model organisms. Here, we report a robust and stable system to allow for clonal expansion of single monkey neuroepithelial stem cells (NESCs) to develop into miniature NT-like structures. Single NESCs can produce functional neurons in vitro, survive, and extensively regenerate neuron axons in monkey brain. NT formation and NESC maintenance depend on high metabolism activity and Wnt signaling. NESCs are regionally restricted to a telencephalic fate. Moreover, single NESCs can turn into radial glial progenitors (RGPCs). The transition is accurately regulated by Wnt signaling through regulation of Notch signaling and adhesion molecules. Finally, using the "NESC-TO-NTs" system, we model the functions of folic acid (FA) on NT closure and demonstrate that FA can regulate multiple mechanisms to prevent NT defects. Our system is ideal for studying NT development and diseases.