The reprogramming factor nuclear receptor subfamily 5, group A, member 2 cannot replace octamer-binding transcription factor 4 function in the self-renewal of embryonic stem cells

FEBS J. 2014 Feb;281(4):1029-45. doi: 10.1111/febs.12665. Epub 2013 Dec 16.


Although octamer-binding transcription factor 4 (Oct-4) is one of the most intensively studied factors in mammalian development, no cellular genes capable of replacing Oct-4 function in embryonic stem (ES) cells have been found. Recent data show that nuclear receptor subfamily 5, group A, member 2 (Nr5a2) is able to replace Oct-4 function in the reprogramming process; however, it is unclear whether Nr5a2 can replace Oct-4 function in ES cells. In this study, the ability of Nr5a2 to maintain self-renewal and pluripotency in ES cells was investigated. Nr5a2 localized to the nucleus in ES cells, similarly to Oct-4. However, expression of Nr5a2 failed to rescue the stem cell phenotype or to maintain the self-renewal ability of ES cells. Furthermore, as compared with Oct-4-expressing ES cells, Nr5a2-expressing ES cells showed a reduced number of cells in S-phase, did not expand normally, and did not remain in an undifferentiated state. Ectopic expression of Nr5a2 in ES cells was not able to activate transcription of ES cell-specific genes, and gene expression profiling demonstrated differences between Nr5a2-expressing and Oct-4-expressing ES cells. In addition, Nr5a2-expressing ES cells were not able to form teratomas in nude mice. Taken together, these results strongly suggest that the gene regulation properties of Nr5a2 and Oct-4 and their abilities to confer self-renewal and pluripotency of ES cells differ. The present study provides strong evidence that Nr5a2 cannot replace Oct-4 function in ES cells.

Keywords: embryonic stem cell; induced pluripotent stem cell; nuclear receptor subfamily 5, group A, member 2 (Nr5a2); octamer-binding transcription factor 4 (Oct-4); self-renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*


  • Nr5a2 protein, mouse
  • Octamer Transcription Factor-3
  • Receptors, Cytoplasmic and Nuclear