Glycosylation in Stem Cell Biology

Embryonic stem cells are pluripotent stem cells originally derived from the inner cell mass of blastocysts and have the essential characteristics of pluripotency and self-renewal. Pluripotent stem cells can differentiate into all of the cell types constituting the adult body. Our current understanding is that pluripotent stem cells transition through three stages: a naïve state, a formative state, and a primed state. The stemness and differentiation of pluripotent stem cells depend on cell-surface glycans, which work as essential modulators in ligand-receptor interactions, cell-cell interactions, and cell-extracellular matrix interactions. Cell-surface glycans bind to various signal ligands, including Wnt, fibroblast growth factors, and bone morphogenetic proteins, and are tissue-specific and developmentally regulated. In addition, intracellular O-linked N-acetylglucosamine, a modification found on only nuclear or cytoplasmic proteins, regulates core transcription factors involved in stemness, phosphorylation of downstream signal components, epigenetics, and liquid-liquid phase separation. Thus, various kinds of glycans regulate each stem cell status; furthermore, different glycan structures at each stage are simultaneously epigenetically regulated by the polycomb repressive complex PRC2. Understanding the functions of glycans in stemness and differentiation is increasingly important for both innovative clinical applications and basic research. This chapter focuses on the roles of glycans in mouse and human pluripotent stem cells.