Sulfated glycosaminoglycans: their distinct roles in stem cell biology

Sulfated glycosaminoglycan (GAG) chains are a class of long linear polysaccharides that are covalently attached to multiple core proteins to form proteoglycans (PGs). PGs are major pericellular and extracellular matrix components that surround virtually all mammalian cell surfaces, and create conducive microenvironments for a number of essential cellular events, such as cell adhesion, cell proliferation, differentiation, and cell fate decisions. The multifunctional properties of PGs are mostly mediated by their respective GAG moieties, including chondroitin sulfate (CS), heparan sulfate (HS), and keratan sulfate (KS) chains. Structural divergence of GAG chains is enzymatically generated and strictly regulated by the corresponding biosynthetic machineries, and is the major driving force for PG functions. Recent studies have revealed indispensable roles of GAG chains in stem cell biology and technology. In this review, we summarize the current understanding of GAG chain-mediated stem cell niches, focusing primarily on structural characteristics of GAG chains and their distinct regulatory functions in stem cell maintenance and fate decisions.