The stem cell niche and tissue biology.

antecedents, what one might refer to as tissue biology (2). Tissue biology, as a field has its own methodological standards for hypothesis generation, experimental design, and data analysis. Indeed the type of data that one obtains for determination of tissue biological effects, although containing molecular and cell biological information, would be different from the other disciplines. One key example of this is the need to view and study intact structures, documenting the structural aspects of the niche through histomorphological images in two or three dimensions. These studies may make use of intact animals exposed to different experimental conditions, but they might also use innovative culture and perfusion techniques to evaluate whole, intact tissue segments ex vivo. Evaluation of such data is photographic, supplemented by histochemical and immunohistochemical staining to highlight different components of anatomical units and cell–matrix relationships. Thus, whereas molecular data usually requires gels and arrays and cell biological data uses images of stained substructures and a variety of means to assess physiological functionality (e.g., by analysis of secreted molecules, changes in molecular composition in cell compartment extracts, measurement of bioelectrical flux), tissue biology examination looks at intact tissues in which structure and arrangement themselves are a form of function. This shift in perspective and tools is in evidence in most of the papers within this volume of Stem Cell Reviews. Proffered papers regarding the stem cell niche of specific organs (kidney, brain, gastrointestinal tract) show photomicroscopy as a central and most potent The stem cell niche is the functional, anatomic location in which stem cells are maintained in quiescent readiness for the occasional need for division and generation of proliferating, repopulating differentiated cell populations. This concept was first elaborated and convincingly demonstrated as more than theory in studies in Drosophila germline production (1). In the Drosophila, ovaryand testes-specific sites (niches) allow the germinal stem cell to divide to produce one daughter cell that remains a stem cell and another daughter cell that differentiates into a transit amplifying cell. Since then such niches have been identified and their components studied in depth in organs with steady turnover of large portions of differentiated cell types needing constant renewal (bone marrow-derived hematopoiesis, skin and adnexal structures, gastrointestinal tract). Subsequent niche investigations have ensued to consider organs, which only recently have been defined as having resident stem cells such as the kidney, brain, and heart. Consideration of the stem cell niche demands a reversal of the standard reductionist progression of studies of biological phenomena as devised during the last centuries. Whereas cell biology and molecular biology are exceptionally successful paradigms for biological studies, the stem cell niche cannot be understood with any degree of completion or complexity without reassembling the bits of data from these lower scale approaches into a whole tissue level system of organization. Thus, while we think of cell biology and molecular biology as defined disciplines, the stem cell niche concept points to the need for re-establishment of a more sophisticated version of their *Correspondence and reprint requests to: