The Function of Glycan Structures for the Maintenance and Differentiation of Embryonic Stem Cells

Various types of glycoprotein and glycolipid are present on the cell surface and function to regulate cell-cell interactions, cell-extracellular matrix interactions, and signals from extrinsic factors, for instance, Wnt, fibroblast growth factor (FGF), Hedgehog (Hh) and bone morphogenetic protein (BMP). The glycan structures on proteins and lipids change dramatically during differentiation. Some of these glycoproteins and glycolipids can be used as markers for the identification of embryonic stem cells (ES cells), such as stage-specific embryonic antigen-1 (SSEA-1) (Atwood et al., 2008; Muramatsu & Muramatsu, 2004), SSEA3, TRA-1-60 antigen and TRA-1-81 antigen (Adewumi et al., 2007). ES cells were originally isolated from the inner cell mass (ICM) of blastocysts and have the essential characteristics of pluripotency and self-renewal. Pluripotency enables the cells to differentiate into all the cell types that constitute the adult body. In 1981, the first mouse ES cell lines were established, and these have proved invaluable as a tool for gene-targeting strategies in mice (Evans & Kaufman, 1981; Martin, 1981). Since the establishment of human ES cell lines in 1998, they have been used in a large number of research studies looking at potential applications for regenerative medicine (Thomson et al., 1998). Thus, ES cells are promising tools for biotechnology and possess key features that should allow their exploitation in the development of cell replacement therapies. To exploit the potential of ES cells for these various purposes, a better understanding of the molecular mechanisms that control self-renewal and pluripotency and also direct differentiation of ES cells is required. Several signaling cascades activated by extrinsic factors such as leukemia inhibitory factor (LIF) (Smith et al., 1988; Williams et al., 1988), BMP (Ying et al., 2003) and Wnt (Miyabayashi et al., 2007; Sasaki et al., 2008; Sato et al., 2004) and the expression of intrinsic factors, such as Oct3/4 and Nanog, maintain self-renewal and pluripotency in ES cells (Boiani & Scholer, 2005). Likewise, Wnt, FGF, Hh and BMP signaling also play key roles in the determination of cell fate during the differentiation of ES cells (Kunath et al., 2007; Sasaki et al., 2009). Proteoglycans are one form of sulfated glycoprotein and consist of several different types of core protein and glycosaminoglycans (sulfated glycans). There are two types of glycosaminoglycan: heparan sulfate (HS) and chondroitin sulfate (CS). They are ubiquitously present on the surface of many different types of cell and are known to play crucial roles in regulating several signaling pathways (Bishop et al., 2007). A large number