Nogo-66 regulates nanog expression through stat3 pathway in murine embryonic stem cells.
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.
Gao
Yuan
Y
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People's Republic of China.
Wang
Bin
B
Xiao
Zhifeng
Z
Chen
Bing
B
Han
Jin
J
Wang
Xia
X
Zhang
Jing
J
Gao
Shaorong
S
Zhao
Yannan
Y
Dai
Jianwu
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000071317:Nanog Homeobox Protein; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013997:Time Factors
D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D009185:Myelin Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse