Transgenic mice with defined combinations of drug-inducible reprogramming factors

Nat Biotechnol. 2009 Feb;27(2):169-71. doi: 10.1038/nbt.1520. Epub 2009 Jan 18.

Abstract

Proviruses carrying drug-inducible Oct4, Sox2, Klf4 and c-Myc used to derive 'primary' induced pluripotent stem (iPS) cells were segregated through germline transmission, generating mice and cells carrying subsets of the reprogramming factors. Drug treatment produced 'secondary' iPS cells only when the missing factor was introduced. This approach creates a defined system for studying reprogramming mechanisms and allows screening of genetically homogeneous cells for compounds that can replace any transcription factor required for iPS cell derivation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Chimera / genetics
  • Chimera / metabolism
  • Doxycycline / pharmacology*
  • Female
  • Fibroblasts / metabolism
  • Genetic Techniques*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Proviruses / genetics
  • Proviruses / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Transcription Factors / drug effects
  • Transcription Factors / genetics*

Substances

  • GKLF protein
  • Kruppel-Like Transcription Factors
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Proto-Oncogene Proteins c-myc
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Transcription Factors
  • Doxycycline