Induced pluripotent stem cells (iPSC) are generated from mouse and human fibroblasts by the introduction of three transcription factors, namely Oct3/4, Sox2, and Klf4. The protooncogene product c-Myc markedly promotes iPSC generation, but it also increases tumor formation in iPSC-derived chimera mice. We herein show that the promotion of iPSC generation by Myc is independent of its transformation property. We found that another Myc family member called L-Myc, as well as c-Myc mutants (W136E and dN2), which all possesses little transformation activity, promoted human iPSC generation more efficiently and specifically than did the wildtype c-Myc. In mice, L-Myc promoted germline transmission, but not tumor formation, in the iPSC-derived chimera mice. These data demonstrated that different functional moieties of the Myc protooncogene products are therefore involved in transformation and promotion of directed reprogramming. All figures were reproduced from PNAS.
Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T., and Yamanaka, S. Promotion of Direct Reprogramming by Transformation-deficient Myc. Proc Natl Acad Sci U S A, 2010 Aug 10;107(32):14152-7. Epub 2010 Jul 26.