This invention relates, in part, to methods and compositions that modulate the stem cell environment. More specifically, the invention relates, in part, to methods and compositions for modulating stem cell differentiation. Such modulation, in some aspects of the invention, is accomplished by agents that modulate glycosaminoglycans in the stem cell microenvironment (i.e., at or on the cell surface and/or in the extracellular matrix). Therefore, methods and compositions are provide for modulating glycosaminoglycan moieties, e.g., heparan sulfate glycosaminoglycan (HSGAG) moieties, in the microenvironment of stem cells. Methods and compositions for promoting or inhibiting embryonic stem cell differentiation (e.g., differentiation into endothelial cells) are also provided. This invention also relates, therefore, in part, to cell populations (e.g., endothelial cell populations or impoverished endothelial cell populations) that can be produced with the methods and compositions provided. Furthermore, the invention relates, in part, to tissues, and uses thereof, formed by the methods and compositions provided. Moreover, the invention also relates, in part, to methods of treatment using the methods and compositions provided.