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LIGHT induces differentiation of mouse embryonic stem cells associated with activation of ERK5

Oncogene volume 25, pages 463–469 (2006)Cite this article

Abstract

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.

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Abbreviations

EB:

embryoid body

ERK:

extracellular signal-regulated kinase

ES cells:

Embryonic stem cells

HVEM:

herpesvirus entry mediator

LIF:

leukemia inhibitory factor

LT-β:

lymphoid toxin-β

LIGHT:

LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells

MKP-3:

MAP kinase phosphatase-3

siRNA:

small interfering RNA

sLIGHT:

soluble LIGHT

SSEA-1:

stage-specific embryonic antigen-1

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Acknowledgements

We thank Martina Berg (University of Iowa) for part of technical assistance and Dr Baoli Yang (University of Iowa) for helpful discussion. Part of this study was performed on Dr Yan Chen's lab in Indiana University (Indianapolis).

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Authors and Affiliations

  1. Department of Internal Medicine, University of Iowa School of Medicine, Iowa City, 52246, IA, USA

    G-M Zou

  2. Department of Medicine, University of Chicago Medical Center, 5841 Maryland Ave., MC2115, Chicago, 60612, IL, USA

    J-J Chen

  3. Shanghai Fuchun Zhongnan Biotech Co. Ltd., Shanghai, 201203, People's Republic of China

    J Ni

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Correspondence to G-M Zou.

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Zou, GM., Chen, JJ. & Ni, J. LIGHT induces differentiation of mouse embryonic stem cells associated with activation of ERK5. Oncogene 25, 463–469 (2006). https://doi.org/10.1038/sj.onc.1208987

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