Stem Cell Fate Decisions: The Role of Heparan Sulfate in the Control of Autocrine and Paracrine Signals

The aim of this review is to explore the idea that the glycosaminoglycan sugar heparan sulfate (HS), richly concentrated on the plasma membrane of all animal cells studied so far and a major component of extracellular matrices, is by virtue of its ability to modulate protein gradients and signal transduction, the master regulator of stem cell fate (and thus wound healing). Moreover, the interaction between HS and members of the TGF-β superfamily is emerging as a central tenet for stem cells. The potential significance of this interaction is best understood by examining both how HS modulates ligand interactions and stability, and how it maintains protein gradients with varying degrees of specificity. Importantly, HS also regulates the activity of numerous antagonists, thus underscoring its importance as a primary regulator of stem cell fate decisions.