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Stem cells are responsible for the growth, homeostasis and repair of many tissues. The maintenance and survival of stem cells is regulated by inputs from their local microenvironment, often referred to as the stem cell
niche. The stem cell niche hypothesis was developed in 1978 by Schofield, who proposed that stem cells reside within fixed compartments, or niches, which are conducive to the maintenance of definitive stem cell properties1. Thus, the niche represents a defined anatomical compartment that provides signals to stem cells in the form of secreted and cell surface molecules to control the rate of stem cell proliferation, determine the fate of stem cell daughters, and protect stem cells from exhaustion or death.
Elegant experiments in model organisms such as worms and flies provided the first visualization of stem cell niches invivo, and subsequent genetic experiments have confirmed the importance of the niche in regulating stem cell behaviour29. Recently, new tools for labelling stem cells insituhave also facilitated the localization and characterization of stem cell niches in mammalian tissues1015. In addition to providing
concrete evidence that niches are essential for proper stem cell function, these studies have revealed that stem cell niches are as varied as the stem cells they support. Moreover, recent work indicates the existence of distinct functional classes of niche, each specialized to sustain the unique functions of particular tissues. Finally, increasing evidence implicates deregulation of the stem cell niche as a proximal cause of many pathologies associated with tissue degeneration16, ageing1720 and tumorigenesis2124.
As discussed below, studies in model organisms such as Drosophilamelanogaster and Caenorhabditiselegans have revealed several features of stem cell niches that are important for controlling stem cell behaviour. First, signals that emanate from the niche regulate stem cell selfrenewal, survival and maintenance23,57. Second,
the particular spatial relationship between stem cells and support cells can polarize stem cells within the niche to promote asymmetric stem cell divisions25,26. Third,
adhesion between stem cells and supporting stromal cells and/or the extracellular matrix (ECM) anchors stem cells within the niche in close proximity to selfrenewal and survival signals27,28. Because recent developments have facilitated the localization and visualization of stem cells within mammalian tissues invivo, it is becoming clear that these key features of stem cell niches are also used...