What does the concept of the stem cell niche really mean today?

Lander et al. BMC Biology 2012, 10:19 http://www.biomedcentral.com/1741-7007/10/19 FORUM Open Access What does the concept of the stem cell niche really mean today? Arthur D Lander, Judith Kimble, Hans Clevers, Elaine Fuchs, Didier Montarras, Margaret Buckingham, Anne L Calof, Andreas Trumpp and Thordur Oskarsson The richness of niche-ness – an introduction Arthur D Lander Ideas about stem cells, and how they behave, have been undergoing a lot of change in recent years, thanks to developments in visualizing, monitoring, and manipulating cells and tissues. Curious to find out what impact these changes are having on one of the most enduring and widely accepted metaphors in stem cell biology – the idea of the stem cell niche – BMC Biology asked researchers working on a variety of systems to write about their current conception of what a stem cell niche really is. The answers presented below suggest that the detailed mechanisms underlying niche function are extremely varied. Niches may be composed of cells, or cells together with extracellular structures such as the extracellular matrix (ECM). They may be sources of secreted or cell surface factors – including members of the Notch, Wnt, fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor (TGF)-β, stem cell factor (SCF), and chemokine families – that control stem cell renewal, maintenance, or survival. They may consist of just a single cell type, or a whole host of interacting cells. They may derive from cells outside the stem cell’s lineage, or they may derive primarily from the stem cell’s own descendents. In general, there seems to be much more consensus about the fact that stem cells invariably need niches than about the specific mechanisms by which niches do their jobs. Why should a stem cell need a special environment? This is a pertinent question, given that none of the elementary processes that stem cells rely upon – growing, dividing, differentiating – are unique to stem cells. We can easily imagine three classes of answers: One possibility is that there are demands placed on stem cells that necessitate special support for viability. For example, the need, imposed by cellular immortality, to minimize the accumulation of genetic damage, may drive stem cells to adopt a peculiar metabolic state that Correspondence: bmcbiologyeditorial@biomedcentral.com might force them to rely upon other cells nearby for sustenance. This ‘nutritive’ function of the niche remains a formal possibility, but in most systems few experimental data in support of it have so far emerged. A second possibility is that niches are agents of feedback control. Recent studies tell us that stem cell pools are not slavishly maintained at a constant size by fixed, asymmetric divisions, but are usually capable of expanding or contracting and, even under homeostatic conditions, may face large stochastic fluctuations. The varied growth factors and cell surface molecules produced by niche cells may share the common goal of controlling stem cell pools. If this is the case, then the niche might best be thought of not simply as an environment conducive to stem cell functioning, but as an apparatus for communicating information about the state of a tissue back to the stem cells that maintain it. An important question to address would then be how niches obtain and relay such information. A third possibility is that niches are instruments of coordination among tissue compartments. Some of the best evidence for this view comes from work on the hair follicle niche, described below by Elaine Fuchs. There, stem and progenitor cells responsible for maintenance of epidermis, pigmentation, hair, and connective and adipose tissue all interact in close proximity. A need to achieve tight coordination among these different cell populations may be the overriding reason for complex organization of this niche. The possibility that other niches may also be hubs of inter-lineage coordination is certainly an idea worth investigating. The C. elegans distal tip cell and the concept of a stem cell niche Judith Kimble Schofield originally hypothesized the existence of a microenvironment required for maintenance of stem cells and coined the term stem cell niche [1] (Figure 1a, left). The first example of such a stem cell niche was the mesenchymal ‘distal tip cell’ (DTC) in Caenorhabditis © 2012 Lander et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.