Proteoglycans in stem cells.

The remarkable promise of pluripotent and multipotent stem cells (SCs) imparts tremendous optimism for advancement of regenerative medicine, developmental biology, and drug discovery. Perhaps the greatest challenge is to finely direct, control, and command their differentiation. As those processes are managed on many levels, including genomic, transcriptomic, and epigenomic, examination of all of these components will yield powerful tools for manipulation of SCs. Carbohydrates surround all cells, including SCs as a glycocalyx. Of particular interest is the class of carbohydrates known as proteoglycans (PGs), which are a diverse group of glycoconjugates consisting of core protein with one or more glycosaminoglycan (GAG) chains attached. They are primarily located in the extracellular matrix as well as at cell surfaces, where they are bound or anchored to the membrane through their core proteins. GAG chains are linear, anionic, and highly heterogeneous carbohydrates consisting of repeating disaccharides. PGs facilitate interaction of cells with the extracellular environment by interacting with chemokines, growth factors, and other signaling molecules. Core proteins are involved in many signaling pathways, both individually, as well as through attached proteins via GAG-mediated interactions. These essential and accessible functions make PGs an excellent target for manipulating SCs and guiding their fate. Studying the role of PGs in cell development will yield valuable insight into the mechanism of SC differentiation and suggest approaches toward directing those pathways. Such studies may also help identify valuable markers for distinguishing between various cell populations during differentiation.