Embryonic stem cell (ESC) fates are governed by a precise set of growth factor signaling events at the stem cell surface. Such events are often orchestrated by heparan sulfate proteoglycans (HSPGs) which template growth factor binding to their corresponding receptors. We report strategies that exploit the function of HSPGs to either promote differentiation or maintain the pluripotency of mouse ESCs. By re-decorating the stem cell glcocalyx with synthetic neoproteoglycans (neoPGs) that bind to fibroblast growth factor 2 (FGF2), we demonstrate that neural specification can be rescued in HSPG-deficient ESCs. We also show that small molecules which antagonize HSPGs can arrest ESCs in a pluripotent state by inhibiting FGF2 binding. Altogether, we demonstrate that the glycocalyx presents a unique opportunity to modulate ESC fates.

Glycocalyx based strategies to modulate embryonic stem cell fates

251st National Meeting (2016)

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