西亚试剂：Promotion of direct reprogramming by transformation-deficie

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.

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