Ratio of Wnt3a to BMP4 doses is critical to their synergistic effects on proliferation of differentiating mouse embryonic stem cells

Authors

  • S.-Y. Lin,

    1. Stem Cell Lab, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan,
    2. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan,
    3. Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan, and
    4. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
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  • C.-L. Chen,

    1. Stem Cell Lab, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan,
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  • Y.-L. Wu,

    1. Stem Cell Lab, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan,
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  • Y.-C. Yang,

    1. Stem Cell Lab, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan,
    2. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan,
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  • Y.-M. Hwu

    1. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan,
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Shyr-Yeu Lin, Stem Cell Lab, Department of Medical Research, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Sec.2, Chung-Shan North Road, Taipei 10449, Taiwan. Tel.: 886 968957410; Fax: 886 2 2523 2448; E-mail: sylin@ms1.mmh.org.tw

Abstract

Abstract.Objectives: To investigate potential interactions between bone morphogenetic protein (BMP) and Wnt signalling on differentiating mouse embryonic stem cells (mESC). Materials and methods: Mouse embryonic stem cells were cultured with differing combinations of Wnt3a, BMP4 and inhibitors of Wnt, BMP, PI-3K (phosphoinositide 3-kinase), p38, ERK1/2 (extracellular signal-regulated kinase 1/2) and JNK (c-Jun N-terminal kinase) pathways. Results: We found that Wnt3a synergized with BMP4 to promote mESC proliferation. Furthermore, the relative ratio of Wnt3a to BMP4 doses was critical to their synergistic effects, which could be abolished by using Dkk-1, noggin or the inhibitors of PI-3K, p38, ERK1/2 and JNK pathways. We also demonstrated that combination of Wnt3a and BMP4 could suppress ectodermal differentiation of mESCs. Moreover, inhibitors of PI-3K, p38, ERK1/2 and JNK pathways could negate this effect. Conclusion: Relative ratio of Wnt3a to BMP4 doses is critical to their synergistic effect on differentiating mESC proliferation, which may work through PI-3K, p38, ERK1/2 and JNK pathways.

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