LIGHT induces differentiation of mouse embryonic stem cells associated with activation of ERK5.
LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) is a recently cloned type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. This cytokine has been extensively defined in its role on T-cell regulation and dendritic cell maturation. However, whether this cytokine regulates stem cell proliferation and/or differentiation remains unknown. In this study, we transduced exogenous LIGHT into embryonic stem cells (ES cells) and found it induced their differentiation. The expression of phospho-STAT3, Nanog and Oct-4 was reduced in LIGHT-transduced ES cells compared with wild-type ES cells. LIGHT-transduced ES cells exhibit a low level of SSEA-1 surface antigen and alkaline phosphatase staining compared with wild-type cells. Introduction of LIGHT into ES cells results in the dephosphorylation of MKP-3 and activation of extracellular signal-regulated kinase (ERK)5. When ERK5 was inhibited by the specific inhibitor PD184352 or knocked down by ERK5 siRNA, reduction of Oct-4 and SSEA-1 expression was rescued. We conclude that LIGHT overrides Leukemia inhibitory factor to induce ES cell differentiation associated with activation of ERK5.
Zou
G-M
GM
Department of Internal Medicine, University of Iowa School of Medicine, Iowa City, IA, USA. gzou@iupui.edu
Chen
J-J
JJ
Ni
J
J
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology*; D004789:Enzyme Activation; D005434:Flow Cytometry; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases