Nogo-66 Regulates Nanog Expression Through Stat3 Pathway in Murine Embryonic Stem Cells

Abstract

Homeodomain transcription factor Nanog plays a critical role in maintaining murine embryonic stem (ES) cells pluripotency. However, its expression regulation largely remains unknown. In this study we show that Nogo receptor (NgR) participates in the regulation of Nanog expression via Stat3 pathway. Activation of NgR results in the phosphorylation of Stat3 and increases expression levels of Nanog mRNA and protein, which inhibits differentiation of embryoid bodies. This up-regulation of Nanog can be abolished by NgR inhibitor PI-PLC and NEP1-40, or phospho-Stat3 inhibitor AG490 and rapamycin. Immunofluorescence assay demonstrates that NgR and its ligand Nogo-A/B exist on mouse blastocysts and cultured ES cells, suggesting NgR might play a role in early embryo development.