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Synergistic effects of FGF-2 and Activin A on early neural differentiation of human pluripotent stem cells

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Abstract

Neural differentiation is an important target of human embryonic stem cells, which provide a source for cell-based therapy, developmental biology, and pharmaceutical research. Previous studies revealed that inhibition of the bone morphogenetic protein is required for neural induction from human embryonic stem cells. On the contrary, the functions of fibroblast growth factors and Activin/Nodal signaling are controversial. Fibroblast growth factor-2 and Activin/Nodal pathways exert divergent influences on human embryonic stem cell concerning the maintenance of both pluripotency and cellular differentiation. We hypothesized that the combination of fibroblast growth factor-2 and Activin A at various concentrations synergistically exerts diverse effects on cell differentiation. To determine the effects of fibroblast growth factor-2 and Activin A on cellular differentiation into neural lineages, we examined the expression of neural differentiation markers in human embryonic stem cells treated with fibroblast growth factor-2 and/or Activin A at various concentrations in a growth factor-defined serum-free medium in short-term culture. In this study, we provide evidence that fibroblast growth factor-2 and Activin A synergistically regulated the initiation of human embryonic stem cell differentiation into neural cell lineages even though human embryonic stem cells autonomously differentiate into neural cell lineages.

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Acknowledgments

We thank Akiko Hamada, Ayaka Fujiki, Mari Wakabayashi, Naoko Ueda, Kaori Okada, and Minako Okamura for an excellent technical support and Takayuki Fukuda for the technical support and discussion. This study was supported by grants-in-aid from the Ministry of Health, Labor and Welfare of Japan to M.K.F.; the Ministry of Education, Culture, Sports, Science, and Technology of Japan to M.K.F., M.S., and M.K.; and the New Energy and Industrial Technology Development Organization (NEDO) of Japan to M.K.F.

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Authors and Affiliations

  1. Laboratory of Stem Cell Cultures, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan

    Sumiyo Mimura, Mika Suga, Yujung Liu, Masaki Kinehara, Kana Yanagihara & Miho K. Furue

  2. Department of Oral Biology & Engineering, Integrated Health Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan

    Sumiyo Mimura & Hiroki Nikawa

  3. Department of Cellular and Molecular Biology, Basic Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan

    Masaki Kinehara

  4. Department of Bioengineering, Nagaoka University of Technology, Niigata, 940-2188, Japan

    Kiyoshi Ohnuma

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  1. Sumiyo Mimura
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  2. Mika Suga
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  3. Yujung Liu
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Correspondence to Miho K. Furue.

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Mimura, S., Suga, M., Liu, Y. et al. Synergistic effects of FGF-2 and Activin A on early neural differentiation of human pluripotent stem cells. In Vitro Cell.Dev.Biol.-Animal 51, 769–775 (2015). https://doi.org/10.1007/s11626-015-9909-8

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  • DOI: https://doi.org/10.1007/s11626-015-9909-8

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