Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14152-7. doi: 10.1073/pnas.1009374107. Epub 2010 Jul 26.
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.
诱导多能干细胞（iPSCs）可通过引入三种转录因子：Oct3/4、Sox2 和 Klf4，从鼠和人成纤维细胞中产生。原癌基因产物 c-Myc 显著促进 iPSC 的产生，但也增加了 iPSC 衍生嵌合小鼠中的肿瘤形成。我们报告说，Myc 促进 iPSC 的产生与其转化特性无关。我们发现 Myc 家族的另一个成员 L-Myc 以及具有很少转化活性的 c-Myc 突变体（W136E 和 dN2）都比 WT c-Myc 更有效地且更特异性地促进人 iPSC 的产生。在小鼠中，L-Myc 促进了 iPSC 衍生嵌合小鼠中的种系传递，但不促进肿瘤形成。这些数据表明，Myc 原癌基因产物的不同功能部分参与了定向重编程的转化和促进。
