7月23日,《自然》在线刊发了中国科学院动物研究所周琪研究员领导的研究组和上海交通大学医学院曾凡一教授领导的研究组共同完成的研究成果,他们首次利用iPS细胞通过四倍体囊胚注射得到存活并具有繁殖能力的小鼠, 从而在世界上第一次证明了iPS细胞的全能性。
利用iPS细胞通过四倍体囊胚注射得到存活并具有繁殖能力的小鼠
iPS细胞全称为诱导性多能干细胞,是由体细胞诱导而成的干细胞,具有和胚胎干细胞类似的发育多潜能性。2006年7月,日本科学家首次宣布发现了将小鼠皮肤细胞转化为多能干细胞的方法,2007年11月,美国和日本科学家将人类细胞诱导为iPS细胞,被《科学》杂志评为2008年世界十大科技进展之首。iPS细胞在生物和医学领域具有广阔的应用前景,有望成为实施再生医学和细胞治疗的重要细胞来源。
iPS的研究突飞猛进,但是iPS细胞是否真正拥有胚胎干细胞一样的全能性? 是否能够真正媲美胚胎干细胞呢?当将胚胎干细胞注射进四倍体的小鼠早期胚胎(没有进一步发育能力,仅提供营养环境的胚胎),再移植入代孕母鼠体内,胚胎干细胞可以发育成正常的小鼠,4倍体囊胚注射方法是验证细胞是否具有全能性的“ 黄金标准” 。但是之前的研究发现,iPS细胞不能像胚胎干细胞一样通过4倍体囊胚注射发育成活体小鼠,iPS细胞注射后形成的小鼠胎儿在怀孕早期至晚期全部死亡,这些结果表明iPS细胞尚不具有全能性。
周琪等制备了37株iPS细胞,利用其中6株iPS细胞系注射了1500多个四倍体胚胎,最终3株iPS细胞系获得了共计27个活体小鼠,经多种分子生物学技术鉴定,证实该小鼠确实从iPS细胞发育而成,有些小鼠现已发育成熟并且繁殖了后代,这是世界上第一次获得完全由iPS细胞制备的活体小鼠,有力地证明了iPS细胞具有真正的全能性。这项工作为进一步研究iPS技术在干细胞、发育生物学和再生医学领域的应用提供了技术平台,将iPS细胞研究推到了新的高度,也为中国在这一国际热点研究领域做出了重要的贡献。(生物谷Bioon.com)
生物谷推荐原始出处:
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.