特异性诱导人诱导多能干细胞向滋养层细胞分化  

Specific inducement of human induced pluripotency cells to trophoblast 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93-98,共6页Journal of International Pathology and Clinical Medicine

摘　　要：目的:通过反转录病毒转染技术成功建立了人诱导分化多能干细胞系(induced pluripotency stem cell,iPSC),并诱导它们向滋养层细胞定向分化,为研究人早期滋养层细胞的发育建立一种新的模型。方法:采用反转录病毒将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)-box2,SOX2]、原癌基因c-Myc和Kruppel样因子4(Kruppel-like factor 4,KLF4)转染到人肺部成纤维细胞中,经过筛选得到重编程后的人iPSC,然后用骨成型蛋白4(bone morphogenetic protein 4,BMP4)将其诱导成为滋养层细胞。结果:通过该病毒转染体系成功获得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,并成功将其诱导分化成为滋养层细胞。结论:通过重编程技术成功建立人iPSC细胞系,并具备与hESC相似的干细胞特性,为进一步研究胚胎早期滋养层细胞发育以及滋养层细胞恶性肿瘤的发生机制提供了一个新的平台。Objective To establish human induced pluripotency stem cell （iPSC） lines by lenti-viral transfection and induce iPSC differentiated to neuroepithelial cells（NECs）, then to create a new model for the study of early neural development of human embryos and provide a new option of treatment to transplant for nerve system disease. Methods Lenti-viral system was used to transfect human lung fibroblast cells with combination of 6 transcription factors：octamer-binding transcription factor-4 （OCT4）, sex determining region Y （SRY）-box 2 （SOX2）, Kruppel-like factor 4 （KLF4）, Nanog homebox（NANOG）, Lin-28 homolog（LIN28） and c-Myc to induce iPSC after screening, then NECs were induced in vitro by adding several growth factors.Results Human iPSC lines were successfully derived from human fibroblast cells which shared the same background and owe similar morphology and pluripotency as human embryonic stem cell （hESC）. iPSC could be induced in vitro to differentiate into neural cells with similar efficiency of differentiation as hESC. Conclusion Human iPSC lines can be derived by lenti-viral system and induced into neural cells, which may be very useful for construction of disease model and understanding the mechanisms for neurological degenerative and neurogenetic diseases.

关 键 词：重编程 人诱导多能干细胞 滋养层细胞 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]