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Cell Res:生殖细胞克隆新技术

2015-03-31 佚名 生物谷

在最近一期的《cell research》杂志上,来自洛克菲勒大学干细胞系的Ali H Brivanlou教授发表了一篇评论文章,主要介绍了最新开发出的一种能够人工诱导人源生殖干细胞的技术。
 
我们都知道生殖细胞是一类十分特殊的细胞类型。在胚胎发育的早期,生殖细胞便已经开始发育:原始生殖细胞(PSC: Primodial Germ Cell,即精子或卵子的前体)在原肠胚时期开始发育。
 
在此之前,由于人源生殖细胞的限制,我们对于生殖细胞的分化方面的研究是建立在小鼠模型的基础上的。而近年来的研究发现,人与鼠的生殖细胞的分化机制存在明显的差异。因此,寻找能够直接研究人类生殖细胞分化的模型就十分重要了。
 
最近由剑桥大学Azim Surani课题组发表在《cell》杂志上的一篇研究提供了一类可以人工诱导胚胎干细胞生成生殖细胞前体的技术。
 
首先,他们以人的胚胎干细胞为研究对象,利用TALEN技术对细胞内部的基因进行编辑:在PGC特异性基因nanos3下游插入了一个红色荧光蛋白基因mCherry,从荧光的表达与否就可以判断PGC nanos3的表达情况。另外,由于之前在小鼠的模型上的研究发现:胚胎干细胞分化程度越低,其被诱导成为生殖细胞前体的成功率就越高。因此,作者们采用了一些相应的培养技术奖人胚胎干细胞诱导到一种分化程度较低的状态。之后,再向这些细胞中加入特定的生长因子,比如BMP2/4,LIF,SCF,EGF,ROCKi等。4到5天后,细胞中有约1/3表达红色荧光,反映了pGC的分化。
 
通过比较诱导后的PGC与其它类型的干细胞的表达谱,作者发现大部分基因的表达水平都十分相近,然而一个叫SOX17的转录因子,被鉴定出在PGC早期具有较高的表达量。另外,SOX17在小鼠的PGC中并没有显著的高表达。这也说明了人与鼠的PGC细胞特征并不相同。
 
这项新技术对于基础科研与临床应用都具有显著的意义:这一第一项成功在体外诱导出生殖细胞前体的技术。由于在人类体外受精以及体细胞核移植试验中,配子都是限制性的因素。这种体外诱导成熟配子的技术能够大大解放以上两种实验的局限性。

原始出处:

Alessia Deglincerti, Ali H Brivanlou.The generation of sex cells FREE.Cell Research,VOLUME 25 ISSUE 3(3,2015): 267-268

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    2015-08-09 维他命
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    2015-07-09 cmn

    mark

    0

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    2015-04-28 aids221
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