Promotion of direct reprogramming by transformation-deficient Myc.
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.
Nakagawa
Masato
M
Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan. nakagawa@cira.kyoto-u.ac.jp
Takizawa
Nanako
N
Narita
Megumi
M
Ichisaka
Tomoko
T
Yamanaka
Shinya
S
D000818:Animals; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D050814:Octamer Transcription Factor-3; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D014170:Transformation, Genetic
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C000715470:MAS1 protein, human; D050814:Octamer Transcription Factor-3; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors