The dynamic glycome microenvironment and stem cell differentiation into vasculature.

The ability to control stem cell differentiation is the holy grail of regenerative medicine. Although significant progress toward this goal has been achieved, few efficient and straightforward methods have been developed, necessitating a better understanding of the mechanisms that influence differentiation. The extracellular microenvironment is emerging as a major player in controlling stem cell fate. Cell surface and secreted heparan sulfate glycosaminoglycans (HSGAGs) are one element of the extracellular matrix that regulates complex cell signaling networks. HSGAGs facilitate binding and availability of cytokines to cells as they progress through development. For example, growth factors such as fibroblast growth factor and vascular endothelial growth factor bind to specific HSGAG sequences during vasculogenesis. HSGAGs have been shown to be critical for stem cell vasculogenesis as well as other differentiation lineages. Understanding the role that the extracellular microenvironment plays in controlling cell fate can lead us closer to directing differentiation for developmental models and regenerative therapies. This review will focus on the role of extracellular microenvironment in regulating cell differentiation, with particular attention to the role of HSGAGs in vasculogenesis.