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《Nature》一日之内竟发5篇有关iPS文章——iPS细胞转化率提高约百倍
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生物谷：http://www.bioon.com/biology/cell/403317.shtml Nature：http://www.nature.com/nature/journal/vaop/ncurrent/index.html 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。 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（哑马拉卡、YAMANAKA）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。 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。 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 Nature advance online publication 9 August 2009 | doi:10.1038/nature08235 Suppression of induced pluripotent stem cell generation by the p53–p21 pathway Hyenjong Hong1,2, Kazutoshi Takahashi1, Tomoko Ichisaka1,3, Takashi Aoi1, Osami Kanagawa4, Masato Nakagawa1,2, Keisuke Okita1 & Shinya Yamanaka1,2,3,5 1 Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan 2 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan 3 Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan 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 5 Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA 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. Letters 1. Suppression of induced pluripotent stem cell generation by the p53–p21 pathwayHyenjong Hong, Kazutoshi Takahashi, Tomoko Ichisaka, Takashi Aoi, Osami Kanagawa, Masato Nakagawa, Keisuke Okita & Shinya Yamanaka doi:10.1038/nature08235 First paragraph | Full Text | PDF (526K) | Supplementary information 2. Linking the p53 tumour suppressor pathway to somatic cell reprogrammingTeruhisa Kawamura, Jotaro Suzuki, Yunyuan V. Wang, Sergio Menendez, Laura Batlle Morera, Angel Raya, Geoffrey M. Wahl & Juan Carlos Izpisúa Belmonte doi:10.1038/nature08311 First paragraph | Full Text | PDF (916K) | Supplementary information 3. The Ink4/Arf locus is a barrier for iPS cell reprogrammingHan Li, Manuel Collado, Aranzazu Villasante, Katerina Strati, Sagrario Ortega, Marta Cañamero, Maria A. Blasco & Manuel Serrano doi:10.1038/nature08290 First paragraph | Full Text | PDF (551K) | Supplementary information 4. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrityRosa M. Marión, Katerina Strati, Han Li, Matilde Murga, Raquel Blanco, Sagrario Ortega, Oscar Fernandez-Capetillo, Manuel Serrano & Maria A. Blasco doi:10.1038/nature08287 First paragraph | Full Text | PDF (778K) | Supplementary information 5. Immortalization eliminates a roadblock during cellular reprogramming into iPS cellsJochen Utikal, Jose M. Polo, Matthias Stadtfeld, Nimet Maherali, Warakorn Kulalert, Ryan M. Walsh, Adam Khalil, James G. Rheinwald & Konrad Hochedlinger doi:10.1038/nature08285 First paragraph | Full Text | PDF (570K) | Supplementary information 1：http://www.nature.com/nature/jou ... bs/nature08285.html http://www.nature.com/nature/jou ... pdf/nature08285.pdf 2：http://www.nature.com/nature/jou ... bs/nature08290.html http://www.nature.com/nature/jou ... pdf/nature08290.pdf 3：http://www.nature.com/nature/jou ... bs/nature08311.html http://www.nature.com/nature/jou ... pdf/nature08311.pdf 4：http://www.nature.com/nature/jou ... bs/nature08287.html http://www.nature.com/nature/jou ... pdf/nature08287.pdf 5：http://www.nature.com/nature/jou ... bs/nature08235.html http://www.nature.com/nature/jou ... pdf/nature08235.pdf [ Last edited by 轩辕之客 on 2009-8-12 at 23:08 ] |
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全部的全文 http://www.stemcell8.cn/viewthre ... p;extra=&page=1 http://www.dxy.cn/bbs/post/view?bid=116&id=15302619&sty=1 [ Last edited by 轩辕之客 on 2009-8-14 at 00:52 ] |
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