. M' m ~: v+ n" A6 `$ l9 W3 Q2 iNo place like home: anatomy and function of the stem cell niche
. y, y$ D1 P. v- c/ P4 LD. Leanne Jones & Amy J. Wagers * B: d6 k, g, P& _. A3 {8 w& w3 C
Nature Reviews Molecular Cell Biology 9, 11-21 (January 2008) | doi:10.1038/nrm2319 / d" S* S# |0 _) {
Abstract
5 ?, _/ z6 w) lStem cells are rare cells that are uniquely capable of both reproducing themselves (self-renewing) and generating the differentiated cell types that are needed to carry out specialized functions in the body. Stem cell behaviour, in particular the balance between self-renewal and differentiation, is ultimately controlled by the integration of intrinsic factors with extrinsic cues supplied by the surrounding microenvironment, known as the stem cell niche. The identification and characterization of niches within tissues has revealed an intriguing conservation of many components, although the mechanisms that regulate how niches are established, maintained and modified to support specific tissue stem cell functions are just beginning to be uncovered.
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The niche is a complex and dynamic structure that transmits and receives signals through cellular and acellular mediators. This schematic depicts a hypothetical niche composite, which summarizes known components of previously described mammalian and non-mammalian niches: the stem cell itself, stromal cells, soluble factors, extracellular matrix, neural inputs, vascular network and cell adhesion components. It is important to note that although many niche components are conserved, it is unlikely that every niche necessarily includes all of the components listed. Instead, niches are likely to incorporate a selection of these possible avenues for communication, specifically adapted to the particular functions of that niche, which might be to provide structural support, trophic support, topographical information and/or physiological cues.* i/ U# b7 b8 \" J# F* q
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Wnt signalling can promote cell proliferation, such as self-renewal of haematopoietic stem cells (HSCs) (a) or proliferation of transit amplifying cells within intestinal crypts (not shown). Within some tissues, however, Wnt signalling directs the differentiation of specific cell lineages, such as hair follicle precursors (b), rather than promoting self-renewal of the multipotent stem cells from the follicular bulge. See the main text and Table 1 for more details. ANG1, angiopoietin-1; BMP4, bone morphogenetic protein-4; EphR, ephrin receptor; GSK3β, glycogen synthase kinase-3β; LEF, lymphoid enhancer factor; OPN, osteopontin; TCF, T-cell factor; TIE2, angiopoietin-1 receptor.9 ]4 ]6 p2 \( J+ t/ B
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Stem cell deficiency or deregulation contributes to multiple human pathologies, and accumulating evidence suggests that therapeutic targeting of the stem cell niche may provide a novel and effective strategy for improving treatment of these disorders. a | For example, correction of ageing- or disease-associated alterations in the niche could be used to boost endogenous stem cell number or function, and thereby improve tissue function17, 19, 115. b | Likewise, enhancing supportive niche function during transplantation could improve the efficiency of engraftment or accelerate stem cell reconstitution, perhaps reducing the number of stem cells needed for effective tissue reconstitution115. c | In addition, because the niche can have an important role in influencing stem cell fate decisions19, 70, as well as promoting stem cell self-renewal, appropriate modification of signals from the niche could be used to alter the outcomes of stem cell differentiation to favour production of a needed cell type or inhibit production of a detrimental one. d | Finally, in light of accumulating evidence suggesting that tumour-propagating cancer stem cells are dependent on signals from their niche22, 23, 114, just like their non-malignant counterparts, therapeutic ablation of components of the cancer stem cell niche could provide a novel strategy to remove tumour support factors, and thus achieve cancer remission.
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发表于 2011-1-22 08:43
发表于 2011-1-22 18:09
