诱导多功能干细胞转化率提高约百倍

细胞海洋

新华网伦敦８月９日电（记者 黄堃）将普通皮肤细胞转化为诱导多功能干细胞（ｉＰＳ细胞）再进行克隆等研究，是近年来干细胞研究的热点领域，但是该领域一直受到细胞转化率太低的制约。英国《自然》杂志网站９日发表最新科研报告说，科学家发现，通过基因路径阻断可以将这一转化的成功率提高约百倍。
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    来自不同国家的５个科研小组同时报告了相关进展，其中包括最先培育出ｉＰＳ细胞的日本科学家山中伸弥的科研小组。科学家发现，通过阻断一个名为“ｐ５３”的基因的路径，可以将皮肤细胞转化为ｉＰＳ细胞的成功率提高至１０％左右，是原有转化率的大约百倍。 1 Z! A8 A' h% k& _) _1 t) g+ P
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    目前，将普通细胞转化为ｉＰＳ细胞的常用方法是通过病毒载体将４个基因注入细胞内；其他一些方法可以只使用２个或３个基因，或者不使用病毒载体，获得的ｉＰＳ细胞会更安全，更少出现不良变异的可能，但是转化率也更低。新发现可以提高所有转化方法的成功率，更好地兼顾效率和安全。 9 o* L( s& s1 R6 c5 l
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    不过科学家提醒说，“ｐ５３”具有抑制细胞癌变、阻止肿瘤生长的作用，因此在通过阻断“ｐ５３”路径提高ｉＰＳ细胞转化率时，也要注意潜在风险。

细胞海洋

Nature advance online publication 9 August 2009 | doi:10.1038/nature08235
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Suppression of induced pluripotent stem cell generation by the p53–p21 pathway6 h9 c6 P- m# [! \* t

' }. A' z+ @7 D+ F/ {Hyenjong Hong1,2, Kazutoshi Takahashi1, Tomoko Ichisaka1,3, Takashi Aoi1, Osami Kanagawa4, Masato Nakagawa1,2, Keisuke Okita1 & Shinya Yamanaka1,2,3,5
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5 d* _& J5 Z8 W( Y1 Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan
# C* l* [' c! I& K; R3 x2 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan9 W( l& t) \- F
3 Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
6 u" L1 _0 ~( f4 Laboratory for Autoimmune Regulation, RIKEN Center for Allergy and Immunology, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
8 _, L: Y4 n4 `5 Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA5 Y$ _4 g. _. t1 j8 p: I
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Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse1, 2, 3, 4 and in human5, 6, 7, 8. The efficiency of this process, however, is low9. Pluripotency can be induced without c-Myc, but with even lower efficiency10, 11. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation12, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53–p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.

轩辕之客

谢谢楼主！2 ?9 `5 D! E/ x
最近好像nature对iPS比较青睐哈！！！

niyou

谢海洋！

cdcliwei

我们目前所从事的工作都是在质上下功夫，如果能在量上多下功夫，控制P53抑制的效率，使其适当表达，一定会得到较好的效果！

pushenglei

iPS必将引起生物学浪潮

jianlindunev

谢谢

tieyun

1# 细胞海洋
( f: A+ g6 n, s: B8 u4 F有全文吗？谢谢

guojingjing

iPS最近成为干细胞研究的热点了，期待能出现实质性的研究成果

gaoyunhezuibang

1# 细胞海洋 ( E, o' ~- N4 J) n1 D# N2 a3 S, z

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