Heparan sulfate control of proliferation and differentiation in the stem cell niche.

Tissue-specific stem cell populations are established in "niches," anatomic locations with precise biochemical and cellular configurations that regulate their release and participation in tissue generation, maintenance, and repair. Niches have evolved to protect and perpetuate the self-renewing, undifferentiated state of the cells within and to regulate the rate of production of committed, tissue-specific progenitors. A niche thus integrates the cell growth, cell adhesion, and cell-cell signals that mediate the balanced response of stem cells to the needs of the organism. One constituent of every niche with the capacity to mediate almost all of the required functions is the glycosaminoglycan sugar heparan sulfate. This sugar is a master regulator of mitogenic and adhesive molecule behavior with the ability to rapidly change its binding affinities on the cell surface. Its properties may be the key to understanding the interplay between stem cells and their niche that creates the dynamic system necessary for sustaining tissues. As such, it has great promise for the design of tissue-specific stem cell therapeutics.