Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NF kappa B and cooperating with Stat3

作者：Torres Josema; Watt Fiona M^*

来源：Nature Cell Biology, 2008, 10(2): 194-U68.

DOI：10.1038/ncb1680

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Self-renewal of mouse ES cells depends on activation of Stat3 by leukaemia inhibitory factor (LIF) in collaboration with bone morphogenetic protein signalling(1-3). The transcription factor Nanog is essential in maintaining pluripotency(4,5) but the mechanisms involved are poorly understood. Here we examine the functional interactions of Nanog with the Stat3 and NF kappa B pathways. Nanog and Stat3 were found to bind to and synergistically activate Stat3-dependent promoters. We also found that Nanog binds to NF kappa B proteins; however, Nanog binding inhibited transcriptional activity of NF kappa B proteins. Endogenous NF kappa B activity and target-gene expression increased during differentiation of ES cells. Overexpression of NF kappa B proteins promoted differentiation, whereas inhibition of NF kappa B signalling, either by genetic ablation of the Ikbkg gene or overexpression of the I kappa B alpha super-repressor, increased expression of pluripotency markers. We conclude that Nanog represses the pro-differentiation activities of NF kappa B and cooperates with Stat3 to maintain pluripotency.

• 出版日期2008-2