Nanog-independent reprogramming to iPSCs with canonical factors

Stem Cell Reports. 2014 Jan 31;2(2):119-26. doi: 10.1016/j.stemcr.2013.12.010. eCollection 2014 Feb 11.

Abstract

It has been suggested that the transcription factor Nanog is essential for the establishment of pluripotency during the derivation of embryonic stem cells and induced pluripotent stem cells (iPSCs). However, successful reprogramming to pluripotency with a growing list of divergent transcription factors, at ever-increasing efficiencies, suggests that there may be many distinct routes to a pluripotent state. Here, we have investigated whether Nanog is necessary for reprogramming murine fibroblasts under highly efficient conditions using the canonical-reprogramming factors Oct4, Sox2, Klf4, and cMyc. In agreement with prior results, the efficiency of reprogramming Nanog (-/-) fibroblasts was significantly lower than that of control fibroblasts. However, in contrast to previous findings, we were able to reproducibly generate iPSCs from Nanog (-/-) fibroblasts that effectively contributed to the germline of chimeric mice. Thus, whereas Nanog may be an important mediator of reprogramming, it is not required for establishing pluripotency in the mouse, even under standard conditions.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cellular Reprogramming / genetics*
  • Chimera / genetics
  • Cluster Analysis
  • Female
  • Fibroblasts / metabolism
  • Gene Expression
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Homeodomain Proteins / genetics*
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Kruppel-Like Factor 4
  • Male
  • Mice
  • Nanog Homeobox Protein
  • Phenotype
  • Transcription Factors / genetics
  • Transcriptome
  • Transduction, Genetic

Substances

  • Homeodomain Proteins
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Transcription Factors