日本京都大學iPS細胞研究所日前發(fā)表公報說,，在培育誘導多能干細胞（iPS細胞）的時候,，使用基因“L－Myc”代替基因“c－Myc”，可大幅降低iPS細胞癌變的風險,，從而有效生成安全的iPS細胞,。
該所教授山中伸彌2007年通過向人體皮膚細胞植入4個基因,，培育出了類似胚胎干細胞的iPS細胞。但4個基因中的“c－Myc”基因有引發(fā)癌癥的危險,。雖然只植入其他3個基因也能培育出iPS細胞,，但是生成的iPS細胞質量較差。
在本次研究中,，山中伸彌率領的研究小組發(fā)現(xiàn),，基因“L－Myc”的結構與“c－Myc”非常相近。為了比較兩種基因的功能,，研究人員分別把這兩種基因搭配其他3種基因一起植入實驗鼠體細胞中,，培育出iPS細胞。然后再令iPS細胞分化成生殖細胞,，并培育出實驗鼠,。約兩年后，用含“c－Myc”基因的iPS細胞培育的實驗鼠有70％以上出現(xiàn)了腫瘤,，而利用“L－Myc”基因的則幾乎未發(fā)現(xiàn)腫瘤,。
同時，新方法培育iPS細胞的效率也比較高,。與使用原先的培育方法相比,，使用新方法可使實驗鼠體細胞轉化為iPS細胞的比例提高到4倍左右，人類體細胞轉化為iPS細胞的比例提高到3倍左右,。與只植入其他3種基因相比,，使用新方法iPS細胞分化成實驗鼠生殖細胞的比例約是前者的5倍。
參與研究的講師中川誠人指出：“這項技術大體上解決了iPS細胞發(fā)育成癌細胞的問題,，具有重要意義,。”（生物谷Bioon.com）
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.1009374107
Promotion of direct reprogramming by transformation-deficient Myc
Masato Nakagawa a , 1 , Nanako Takizawa a , Megumi Narita a , b , Tomoko Ichisaka a , b , and Shinya Yamanaka a , b , c , d , 1
aCenter for iPS Cell Research and Application and
bInstitute for Integrated Cell–Material Sciences, Kyoto University, Kyoto 606-8507, Japan;
cYamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan; and
d Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158
Induced pluripotent stem cells (iPSCs) are generated from mouse and human fibroblasts by the introduction of three transcription factors: Oct3/4, Sox2, and Klf4. The proto-oncogene product c-Myc markedly promotes iPSC generation, but also increases tumor formation in iPSC-derived chimeric mice. We report that the promotion of iPSC generation by Myc is independent of its transformation property. We found that another Myc family member, L-Myc, as well as c-Myc mutants (W136E and dN2), all of which have little transformation activity, promoted human iPSC generation more efficiently and specifically compared with WT c-Myc. In mice, L-Myc promoted germline transmission, but not tumor formation, in the iPSC-derived chimeric mice. These data demonstrate that different functional moieties of the Myc proto-oncogene products are involved in the transformation and promotion of directed reprogramming.
