A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages

Nat Cell Biol. 2013 Jun;15(6):579-90. doi: 10.1038/ncb2742. Epub 2013 Apr 30.


Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated the role of Oct4 using the process of induced pluripotency. We found that a defined embryonic stem cell (ESC) level of Oct4 is required for pluripotency entry. However, once pluripotency is established, the Oct4 level can be decreased up to sevenfold without loss of self-renewal. Unexpectedly, cells constitutively expressing Oct4 at an ESC level robustly differentiated into all embryonic lineages and germline. In contrast, cells with low Oct4 levels were deficient in differentiation, exhibiting expression of naive pluripotency genes in the absence of pluripotency culture requisites. The restoration of Oct4 expression to an ESC level rescued the ability of these to restrict naive pluripotent gene expression and to differentiate. In conclusion, a defined Oct4 level controls the establishment of naive pluripotency as well as commitment to all embryonic lineages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage
  • Cells, Cultured
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Profiling
  • Gene Knockout Techniques
  • Homeodomain Proteins / genetics
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Nanog Homeobox Protein
  • Neural Stem Cells
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism*


  • Homeodomain Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse