特异性诱导人诱导多能干细胞向神经上皮细胞分化  

Specific inducement of human induced pluripotency stem cells to neuroepithelial cells

作　　者：郭敏[1,2] 曾辉[3,4] 柳林欣[3] 袁小瑜[3] 林戈[4,5] 王光平[3] 李学君[2] 徐仁和[4] 陈方平[3] 刘慧霞[1] 

机构地区：[1]中南大学湘雅医院老年病科,长沙410008 [2]康涅狄格大学神经生物系,美国康涅狄格州法明顿市06030 [3]中南大学湘雅医院血液科,长沙410008 [4]康涅狄格大学遗传与发育生物学系,美国康涅狄格州法明顿市06030 [5]中南大学生殖与干细胞工程研究所,长沙410078

出　　处：《国际病理科学与临床杂志》2010年第2期99-105,共7页Journal of International Pathology and Clinical Medicine

摘　　要：目的:通过慢病毒转染技术成功建立了人诱导分化多能干细胞系(induced pluripotent stem cell,iPSC)并诱导它们向神经上皮细胞(neuroepithelial cells,NECs)定向分化,为研究人胚胎早期神经发育建立一种新的模型,并有望为临床神经系统病变的治疗提供一种新的移植选择。方法:采用慢病毒将转录因子八聚体结合转录因子-4(octamer-binding transcription factor-4,OCT4)、性别决定Y区域转录因子2[sex determining region Y(SRY)-box 2,SOX2]、Nanog同源盒(Nanog homebox,NANOG)、Lin-28同源因子(Lin-28 homolog,LIN28)、原癌基因c-Myc和Kruppel样因子4(Kruppel-like factor 4,KLF4)导入到人胎肺成纤维细胞中,经过筛选得到重编程后的人iPSC,并在体外通过加入数种生长因子将其诱导成为NECs。结果:成功获得与成纤维细胞相同遗传背景的iPSC,具有与人胚干细胞(human embryonic stem cell,hESC)相似的形态学及多向分化潜能,且能在体外被诱导分化成为NECs,分化效率与hESC相似。结论:通过重编程技术成功建立人iPSC并将其定向诱导分化为NECs,为iPSC在神经系统疾病特别是遗传性或退行性神经病变的治疗和机制研究中的应用推广奠定了实验基础。Objective To establish human induced pluripotency stem cell（iPSC） lines by retroviral transfection and induce iPSC differentiated to trophoblast cells, which provide a new method for setting up a developmental model of trophoblast.Methods Human lung fibroblast cells （IMR-90） were transfec-ted with combination of 4 transcription factors： octamer-binding transcription factor-4（OCT4）, sex determining region Y （ SRY ）-box 2 （Sox2）, c-Myc, Kruppel-like factor 4 （Klf4） by retroviral system. The iPSC clones were selected after reprogrammed from fibroblast cells, and then they were induced to trophoblast with BMP4 treatment.Results Multiple human iPSC lines were successfully derived by retroviral system, and the cells shared the similarity with human embryonic stem cells in both morphology and pluripotency. Conclusion Human iPSC lines are derived by retroviral system, which provide a useful platform for the further study of early trophoblast development and the mechanism of trophoblast related malignant diseases.

关 键 词：重编程 人诱导多能干细胞 神经上皮细胞 

分 类 号：R741[医药卫生—神经病学与精神病学]