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Lewis X-Carrying Neoglycolipids Evoke Selective Apoptosis in Neural Stem Cells

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Abstract

N-glycans carrying the Lewis X trisaccharide [Galβ1-4 (Fucα1-3) GlcNAc] are expressed by neural stem cells (NSCs) exclusively before differentiation, and they actively contribute to the maintenance of stemness of these cells. To address the functional roles of the Lewis X-mediated molecular interactions in NSCs, we created a series of synthetic neoglycolipids that contained a Lewis X-carrying glycan connected to an acyl chain through an amide bond. The neoglycolipids formed aqueous micelles displaying functional Lewis X glycotopes. Surprisingly, the neoglycolipid micelles evoked selective apoptosis in undifferentiated NSCs, whereas their differentiated cells remained unaffected. The apoptotic activity depended on the structural integrity of the Lewis X glycotopes and also on the length of the acyl chain, with an optimum length of C18. We propose hypothetical functional mechanisms of the neoglycolipid, which involves selective NSC targeting with Lewis X glycan and apoptotic signaling by the intracellular release of fatty acids. This serendipitous finding may offer a new strategy for controlling neural cell fates using artificial glycoclusters.

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Acknowledgements

This study was supported by Grants-in-Aid for Scientific Research (C) (JP15K07935 to H.Y.), Challenging Exploratory Research (JP26560451 to K.K.), and Scientific Research on Innovative Areas (JP26110716 and JP17H06414 to H.Y. and JP25102008 to K.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Agency for Medical Research and Development (to H.Y.) and Grant for Basic Science Research Projects from The Sumitomo Foundation (to T.Y.).

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Author notes

  1. Hirokazu Yagi and Gengwei Yan have contributed equally to this work.

Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan

    Hirokazu Yagi, Shingo Tsuge, Takumi Yamaguchi & Koichi Kato

  2. Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787, Japan

    Gengwei Yan, Tatsuya Suzuki, Takumi Yamaguchi & Koichi Kato

  3. School of Physical Science, SOKENDAI (The Graduate University for Advanced Studies), 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787, Japan

    Gengwei Yan & Koichi Kato

  4. School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, 923-1292, Japan

    Gengwei Yan & Takumi Yamaguchi

Authors
  1. Hirokazu Yagi
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  2. Gengwei Yan
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Correspondence to Hirokazu Yagi or Koichi Kato.

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Yagi, H., Yan, G., Suzuki, T. et al. Lewis X-Carrying Neoglycolipids Evoke Selective Apoptosis in Neural Stem Cells. Neurochem Res 43, 212–218 (2018). https://doi.org/10.1007/s11064-017-2415-5

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  • DOI: https://doi.org/10.1007/s11064-017-2415-5

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