將普通皮膚細胞轉(zhuǎn)化為誘導多能干細胞（iPS細胞）再進行克隆等研究，是近年來干細胞研究的熱點領(lǐng)域,，但是該領(lǐng)域一直受到細胞轉(zhuǎn)化率太低的制約,。英國《自然》雜志網(wǎng)站9日發(fā)表最新科研報告說,，科學家發(fā)現(xiàn),，通過基因路徑阻斷可以將這一轉(zhuǎn)化的成功率提高約百倍。
來自不同國家的5個科研小組同時報告了相關(guān)進展,，其中包括最先培育出iPS細胞的日本科學家山中伸彌的科研小組,。科學家發(fā)現(xiàn),，通過阻斷一個名為“p53”的基因的路徑,，可以將皮膚細胞轉(zhuǎn)化為iPS細胞的成功率提高至10％左右，是原有轉(zhuǎn)化率的大約百倍,。
目前,，將普通細胞轉(zhuǎn)化為iPS細胞的常用方法是通過病毒載體將4個基因注入細胞內(nèi)；其他一些方法可以只使用2個或3個基因,，或者不使用病毒載體,，獲得的iPS細胞會更安全，更少出現(xiàn)不良變異的可能,，但是轉(zhuǎn)化率也更低,。新發(fā)現(xiàn)可以提高所有轉(zhuǎn)化方法的成功率，更好地兼顧效率和安全,。
不過科學家提醒說,，“p53”具有抑制細胞癌變、阻止腫瘤生長的作用,，因此在通過阻斷“p53”路徑提高iPS細胞轉(zhuǎn)化率時,，也要注意潛在風險。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
