中文摘要
神经类退行性疾病给患者及其亲属带来了巨大的不幸,目前尚未有可行的治愈方案。人类胚胎干细胞因为具有多胚层的分化潜能而成为细胞替代治疗研究的珍贵资源细胞。但目前对人胚胎干细胞进行神经分化的机制尚未完全解析,从而导致分化效率极低,因此需要寻求一个高效和严谨的策略对神经分化的调控机制进行进一步的研究探索。找到调控神经分化的关键基因和网络,对于提高神经分化效率,获取大量可用于细胞替代治疗细胞的具有巨大的推动作用和实用价值。本研究拟通过基因编辑技术在人胚胎干细胞上标记神经干细胞报告基因,然后借助全基因组的向导RNA库和CRISPR技术对人胚胎干细胞进行遗传学筛选,最终获得调控神经分化的关键基因列表,解析神经分化的关键机制。
英文摘要
Degenerative diseases bring great misfortune to patients and their families, and there is no effective method to cure. Human embryonic stem cells (hESCs) are valuable cell resources in cell replacing therapies research for holding multiple differentiation potentials to three germ layers. However, the mechanism underlying neural differentiation of hESCs is not clarified clearly yet, resulting in the low efficiency. It is important to find a efficient and strict strategy to uncover the regulation mechanism of neural differentiation. The discovery of key genes and pathway could improve efficiency and help to obtain more neural lineage cells, which would push forward the research of cell-replacement therapies. This project will mark hESCs with neural stem cells specific marker genes by genomic editing technology, and screen the vital differentiation genes in these reporter hESCs via CRISPR system and whole-scale guide RNA library, figuring out essential mechanism behind neural differentiation.
