日本京都大学iPS细胞研究所日前发表公报说，在培育诱导多能干细胞（iPS细胞）的时候，使用基因“L－Myc”代替基因“c－Myc”，可大幅降低iPS细胞癌变的风险，从而有效生成安全的iPS细胞。
该所教授山中伸弥2007年通过向人体皮肤细胞植入4个基因，培育出了类似胚胎干细胞的iPS细胞。但4个基因中的“c－Myc”基因有引发癌症的危险。虽然只植入其他3个基因也能培育出iPS细胞，但是生成的iPS细胞质量较差。
在本次研究中，山中伸弥率领的研究小组发现，基因“L－Myc”的结构与“c－Myc”非常相近。为了比较两种基因的功能，研究人员分别把这两种基因搭配其他3种基因一起植入实验鼠体细胞中，培育出iPS细胞。然后再令iPS细胞分化成生殖细胞，并培育出实验鼠。约两年后，用含“c－Myc”基因的iPS细胞培育的实验鼠有70％以上出现了肿瘤，而利用“L－Myc”基因的则几乎未发现肿瘤。
同时，新方法培育iPS细胞的效率也比较高。与使用原先的培育方法相比，使用新方法可使实验鼠体细胞转化为iPS细胞的比例提高到4倍左右，人类体细胞转化为iPS细胞的比例提高到3倍左右。与只植入其他3种基因相比，使用新方法iPS细胞分化成实验鼠生殖细胞的比例约是前者的5倍。
参与研究的讲师中川诚人指出：“这项技术大体上解决了iPS细胞发育成癌细胞的问题，具有重要意义。”（生物谷Bioon.com）
生物谷推荐原文出处：
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.
