Glycobiology of neural stem cells

The mammalian central nervous system is organized by a variety of cells, such as neurons and glial cells, that are generated from a common progenitor, the neural stem cell (NSC). NSCs are defined as undifferentiated neural cells that are characterized by their high proliferative potential while retaining the capacity for self-renewal and multipotency. NSCs and their progeny may be distinguished by the expression of glycoconjugates (e.g., glycoproteins, glycolipids, and proteoglycans). The carbohydrate antigens carried by glycoconjugates are mainly localized on the plasma membrane surface of the cells and they serve as excellent biomarkers for various stages of cellular differentiation. Thus, they have been utilized as ligands for sorting NSCs or their progeny by cell cytometry. Methods have been established for utilizing polysialic acid-neural cell adhesion molecule (PSA-NCAM), stage-specific embryonic antigen-1 (SSEA-1), and gangliosides for cell sorting. Furthermore, glycoconjugates have also been suggested to have a wide range of receptor and signaling functions in NSCs. For example, basic fibroblast growth factor, an important mitogen of NSCs, requires heparan sulfate proteoglycans and glycosylated cystatin C for activity. Notch signaling, which regulates a wide variety of developmental processes in various cells including NSCs, is modulated by the O-fucose glycan modification. In peripheral nervous system (PNS), the human natural killer-1 (HNK-1) antigen regulates the migration of neural crest cells, cell populations containing the stem cells. Thus, glycoconjugates serve not only as marker molecules, but also as functional molecules as well. In the present review, we discuss the expression pattern and possible functions of glycoconjugates in NSCs.