An important aspect of stem cell research is the function of the cells that support them and enable them to function properly. These systems of supportive cells — called niches — sequester stem cells from apoptotic and differentiation stimuli and prevent excessive stem cell production, which could lead to tumor initiation and growth. Niches also help stem cells maintain a balance between inactivation and activation. In a review of the interactions between stem cells and niches, Kateri A. Moore and Ihor R. Lemischka of Princeton University’s department of molecular biology in New Jersey focus on the stem cell systems of the intestinal epithelium, the epidermis and bone marrow. They note that several themes have emerged during the study of these systems. One is that anatomical organization manages the spatiotemporal functions of stem cells, which is most apparent in the stem cells in the intestines and in hair follicles. In addition, positive and negative cellular signaling are integrated within the niches, and intercellular signaling pathways are shared by the niche components. According to the authors, among the challenges for ongoing research efforts is the development of effective real-time imaging techniques that can analyze stem cell behavior in vitro and niche behavior in vivo. Other challenges include the development of equivalent definitions and assay systems for all three stem cell systems, achieving a more complete understanding of niche cell signaling pathways, the creation of in vitro systems that accurately replicate the in vivo functions of niches, and the elucidation of how niche signals are coupled with cell cycle regulation and other processes, and of how niches are changed by stress or pathology. The reviewers also briefly describe the roles played by laser capture technology and by fluorescence microscopy in stem and niche cell research. (Science, March 31, 2006, pp. 1880-1885.)