近日,,上海交通大學(xué)馮立新研究小組報(bào)道一個(gè)全新的體外誘導(dǎo)精子和卵子的方法,。馮立新研究員采用的方法可從雄性胚胎干細(xì)胞(XY 染色體)在體外同時(shí)生成游動(dòng)的精子和卵子,。更為重要的是他們的研究進(jìn)一步闡明了從胚胎干細(xì)胞生成精子和卵子分子機(jī)理,是這一領(lǐng)域研究的重大突破。
之前,,科學(xué)家們已經(jīng)證明了胚胎干細(xì)胞(ESC)能在體外分化出胚性生殖細(xì)胞,,馮立新研究小組體外誘導(dǎo)分化并不經(jīng)過類胚體形成,通過利用轉(zhuǎn)基因技術(shù)直接從胚胎干細(xì)胞轉(zhuǎn)化為生殖細(xì)胞,。Dazl基因是表達(dá)生殖細(xì)胞特異RNA結(jié)合蛋白的基因,,人和多種動(dòng)物的Dazl基因是精子發(fā)生的重要調(diào)控因子,Dazl基因突變或表達(dá)缺乏將導(dǎo)致精子發(fā)生過程減數(shù)分裂障礙和雄性不育,。研究者通過Dazl基因的異位表達(dá),,最終在體外將小鼠胚胎干細(xì)胞同時(shí)誘導(dǎo)出了游動(dòng)的精子和卵子。此外,, Dazl基因的瞬時(shí)過量表達(dá)使Nanog受到抑制,,但是小鼠胚胎干細(xì)胞核抗原被誘導(dǎo)成生殖細(xì)胞。Dazl基因敲低導(dǎo)致了生殖細(xì)胞部分標(biāo)記物基因表達(dá)降低,,比如說Stella,,MVH和Prdm1等。馮立新研究小組不僅證明了Dazl基因是控制生殖細(xì)胞分化的一個(gè)主要控制基因,,而且通過Dazl基因異位表達(dá)誘導(dǎo)出小鼠胚胎干細(xì)胞在體外分化成了生殖細(xì)胞精子和卵子,。
2009年10月28日,斯坦福大學(xué)人類胚胎干細(xì)胞及再生組織醫(yī)學(xué)研究小組Kehkooi Kee 等在Nature發(fā)表了他們最新的研究成果,,研究者在實(shí)驗(yàn)室通過人體干細(xì)胞制造出人工精子和卵子,,這一研究成果進(jìn)一步證實(shí)了馮立新研究團(tuán)隊(duì)所做的工作的前沿性和重要性,同時(shí)也表明我國在體外誘導(dǎo)干細(xì)胞生成精子和卵子研究處于國際領(lǐng)先地位,。(生物谷Bioon.com)
馮立新研究員參加“干細(xì)胞之春系列活動(dòng)——干細(xì)胞技術(shù)與應(yīng)用講座”并作精彩報(bào)告
Nature:利用干細(xì)胞培育出人工精子卵子
生物谷推薦原始出處:
Journal of Molecular Cell Biology (2009), 1–11 doi:10.1093/jmcb/mjp026
Dazl Promotes Germ Cell Differentiation from Embryonic Stem Cells
Zhuo Yu1, Ping Ji1, Jinping Cao1, Shu Zhu1, Yao Li2, Lin Zheng3, Xuejin Chen2, and Lixin Feng1,*
1 Laboratory for Germ Cell Research, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2 Department of Laboratory Animal Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3 Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
It has been demonstrated that through the formation of embryoid bodies (EBs) germ cells can be derived from embryonic stem (ES) cells. Here, we describe a transgene expression approach to derive germ cells directly from ES cells in vitro without EB formation. Through the ectopic expression of Deleted in Azoospermia-Like (Dazl), a germ cell-specific RNA-binding protein,both motile tailed-sperm and oocytes were induced from mouse ES (mES) cells in culture. Furthermore, transient overexpression of Dazl led to suppression of Nanog but induced germ cell nuclear antigen in mES cells. Dazl knockdown resulted in reduction in the expression of germ cell markers including Stella, MVH and Prdm1. Our study indicates that Dazl is a master gene controlling germ cell differentiation and that ectopic expression of Dazl promotes the dynamic differentiation of mouse ES cells into gametes in vitro.