Lewis X-Carrying Neoglycolipids Evoke Selective Apoptosis in Neural Stem Cells
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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.
KeywordsNeural stem cell Lewis X Neoglycolipid Apoptosis
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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Conflict of interest
The authors declare that they have no conflict of interest.
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