Promotion of direct reprogramming by transformation-deficient Myc

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cellular Reprogramming*
  • Fibroblasts / cytology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Kruppel-Like Transcription Factors
  • Mice
  • Octamer Transcription Factor-3
  • Proto-Oncogene Proteins c-myc / physiology*
  • SOXB1 Transcription Factors
  • Transcription Factors / genetics*
  • Transformation, Genetic

Substances

  • GKLF protein
  • Kruppel-Like Transcription Factors
  • Octamer Transcription Factor-3
  • Proto-Oncogene Proteins c-myc
  • SOXB1 Transcription Factors
  • Transcription Factors