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Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14152-7. doi: 10.1073/pnas.1009374107. Epub 2010 Jul 26.

Promotion of direct reprogramming by transformation-deficient Myc.

Author information

  • 1Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan. nakagawa@cira.kyoto-u.ac.jp

Abstract

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.

PMID:
20660764
[PubMed - indexed for MEDLINE]
PMCID:
PMC2922531
Free PMC Article

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