7月23日,,《自然》在線刊發(fā)了中國(guó)科學(xué)院動(dòng)物研究所周琪研究員領(lǐng)導(dǎo)的研究組和上海交通大學(xué)醫(yī)學(xué)院曾凡一教授領(lǐng)導(dǎo)的研究組共同完成的研究成果,他們首次利用iPS細(xì)胞通過(guò)四倍體囊胚注射得到存活并具有繁殖能力的小鼠,, 從而在世界上第一次證明了iPS細(xì)胞的全能性,。
利用iPS細(xì)胞通過(guò)四倍體囊胚注射得到存活并具有繁殖能力的小鼠
iPS細(xì)胞全稱為誘導(dǎo)性多能干細(xì)胞,是由體細(xì)胞誘導(dǎo)而成的干細(xì)胞,,具有和胚胎干細(xì)胞類似的發(fā)育多潛能性,。2006年7月,,日本科學(xué)家首次宣布發(fā)現(xiàn)了將小鼠皮膚細(xì)胞轉(zhuǎn)化為多能干細(xì)胞的方法,2007年11月,,美國(guó)和日本科學(xué)家將人類細(xì)胞誘導(dǎo)為iPS細(xì)胞,,被《科學(xué)》雜志評(píng)為2008年世界十大科技進(jìn)展之首。iPS細(xì)胞在生物和醫(yī)學(xué)領(lǐng)域具有廣闊的應(yīng)用前景,,有望成為實(shí)施再生醫(yī)學(xué)和細(xì)胞治療的重要細(xì)胞來(lái)源,。
iPS的研究突飛猛進(jìn),但是iPS細(xì)胞是否真正擁有胚胎干細(xì)胞一樣的全能性,? 是否能夠真正媲美胚胎干細(xì)胞呢,?當(dāng)將胚胎干細(xì)胞注射進(jìn)四倍體的小鼠早期胚胎(沒(méi)有進(jìn)一步發(fā)育能力,僅提供營(yíng)養(yǎng)環(huán)境的胚胎),,再移植入代孕母鼠體內(nèi),,胚胎干細(xì)胞可以發(fā)育成正常的小鼠,4倍體囊胚注射方法是驗(yàn)證細(xì)胞是否具有全能性的“ 黃金標(biāo)準(zhǔn)” ,。但是之前的研究發(fā)現(xiàn),,iPS細(xì)胞不能像胚胎干細(xì)胞一樣通過(guò)4倍體囊胚注射發(fā)育成活體小鼠,iPS細(xì)胞注射后形成的小鼠胎兒在懷孕早期至晚期全部死亡,,這些結(jié)果表明iPS細(xì)胞尚不具有全能性,。
周琪等制備了37株iPS細(xì)胞,利用其中6株iPS細(xì)胞系注射了1500多個(gè)四倍體胚胎,,最終3株iPS細(xì)胞系獲得了共計(jì)27個(gè)活體小鼠,,經(jīng)多種分子生物學(xué)技術(shù)鑒定,證實(shí)該小鼠確實(shí)從iPS細(xì)胞發(fā)育而成,,有些小鼠現(xiàn)已發(fā)育成熟并且繁殖了后代,,這是世界上第一次獲得完全由iPS細(xì)胞制備的活體小鼠,有力地證明了iPS細(xì)胞具有真正的全能性,。這項(xiàng)工作為進(jìn)一步研究iPS技術(shù)在干細(xì)胞,、發(fā)育生物學(xué)和再生醫(yī)學(xué)領(lǐng)域的應(yīng)用提供了技術(shù)平臺(tái),將iPS細(xì)胞研究推到了新的高度,,也為中國(guó)在這一國(guó)際熱點(diǎn)研究領(lǐng)域做出了重要的貢獻(xiàn),。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature advance online publication 23 July 2009 | doi:10.1038/nature08267
iPS cells produce viable mice through tetraploid complementationnear-final version
Xiao-yang Zhao1,2,5, Wei Li1,2,5, Zhuo Lv1,2,5, Lei Liu1, Man Tong1,2, Tang Hai1, Jie Hao1,2, Chang-long Guo1,2, Qing-wen Ma3, Liu Wang1, Fanyi Zeng3,4 & Qi Zhou1
1 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2 Graduate School of Chinese Academy of Sciences, Beijing 100049, China
3 Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China
4 Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
5 These authors contributed equally to this work.
6 Correspondence to: Fanyi Zeng3,4Qi Zhou1 Correspondence and requests for materials should be addressed to Q.Z.
Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat1, 2, 3, 4, 5, 6. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells7, 8. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.