Heparan sulfate biosynthesis enzymes in embryonic stem cell biology

Embryonic stem (ES) cells are derived from the inner cell mass of the blastocyst and can give rise to all cell types in the body. The fate of ES cells depends on the signals they receive from their surrounding environment, which either promote self-renewal or initiate differentiation. Heparan sulfate proteoglycans are macromolecules found on the cell surface and in the extracellular matrix. Acting as low-affinity receptors on the cell surface, heparan sulfate (HS) side chains modulate the functions of numerous growth factors and morphogens, having wide impact on the extracellular information received by cells. ES cells lacking HS fail to differentiate but can be induced to do so by adding heparin. ES cells defective in various components of the HS biosynthesis machinery, thus expressing differently flawed HS, exhibit lineage-specific effects. Here we discuss recent studies on the biological functions of HS in ES cell developmental processes. Since ES cells have significant potential applications in tissue/cell engineering for cell replacement therapies, understanding the functional mechanisms of HS in manipulating ES cell growth in vitro is of utmost importance, if the stem cell regenerative medicine from scientific fiction ever will be made real.