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。 2 x1 s! d9 N& b- D( v

; O/ Q5 z5 r5 ]3 z+ x3 `    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。 ) y# s2 w: t# \. x% ~5 e
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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。
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8 g* p: p) n5 _+ G6 g( p    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) i" b* m- ?* a9 f- n* E
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Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
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. K- }/ g% k" Q1 p1 \9 K1 ~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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1 Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan7 r$ q6 H5 n! {, \5 ^0 x0 s
2 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
2 d. I" J4 W5 Q0 D% A0 q" ]% }( K6 x3 Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
1 ~7 `0 k# J0 V$ A. C1 ?+ _4 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
) r  i: U  D  Z' l' N5 Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA* O- g; @: q) J# A3 _% d5 f$ k

; R$ j: L/ Y9 b9 n  c# R, ?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！
! n4 C/ ?) r9 z* l" ]6 q  g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

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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
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