In many contexts, self-renewal and differentiation of stem cells are influenced by signals from their environment, constituting a niche. It is postulated that stem cells compete for local growth factors in the niche, thereby maintaining a balance between the numbers of self-renewing and differentiated cells. A critical aspect of the niche model for stem cell regulation is that the availability of self-renewing factors is limited and that stem cells compete for these factors (Fig. 1). Consequently, the range and concentrations of the niche factors are of critical importance. Now that some of the few self-renewing factors have become identified, aspects of the niche models can be tested experimentally. In this chapter, we address mechanisms of signal regulation that take place at the level of signal-producing cells, constituting a niche for stem cells. We emphasize the biochemical properties and posttranslational modifications of the signals, all in the context of Wnt signaling. We propose that these modifications control the range of Wnt signaling and have critical roles in establishing niches for stem cells in various tissues.