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。 7 w7 v: i9 C9 X! R" w

& n6 {  v* X$ d    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。 - T$ Q; C% t/ k  d& c

! U  ?! d" @2 d) G    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。 5 a0 |0 V5 h% l6 f# K0 w& o9 t

2 V( j0 k4 `- c# Z; }    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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3 [1 k2 I* G* e5 @& q3 ESuppression of induced pluripotent stem cell generation by the p53–p21 pathway
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. l8 {2 R4 l- n0 D  Q2 p% S4 v$ jHyenjong 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, Japan
0 t& l, p0 Z+ m: s3 Y" u2 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan6 p- _4 o& J8 m
3 Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan' |5 b& O% Y. U3 h( H) q7 s
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
; g( T) ?; X" D# e# e3 d$ b# K5 Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
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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.