Radford I R, Lobachevsky P N
South Yarra, Victoria, Australia.
Cell Prolif. 2006 Oct;39(5):403-14. doi: 10.1111/j.1365-2184.2006.00396.x.
We have shown that the kinetics of conversion of intestinal crypt cell populations to a partially or wholly mutant phenotype are consistent with a model in which each crypt contains an infrequently dividing 'deep' stem cell that is the progenitor of several more frequently dividing 'proximate' stem cells. An assumption of our model is that each deep stem cell exists in a growth inhibitory niche. We have used information from the literature to develop a model for a quiescent intestinal stem cell niche. This niche is postulated to be primarily defined by an enteroendocrine cell type that maintains stem cell quiescence by secretion of growth inhibitory peptides such as somatostatin and guanylin/uroguanylin. Consistent with this model, there is evidence that the proteins postulated as defining a growth-inhibitory stem cell niche can act as intestinal tumour suppressors. Confirmation that a growth-inhibitory niche does exist would have important implications for our understanding of intestinal homeostasis and tumorigenesis.
我们已经表明，肠道隐窝细胞群体转变为部分或完全突变表型的动力学与一个模型一致，在该模型中，每个隐窝都包含一个不常分裂的“深层”干细胞，它是几个更频繁分裂的“近端”干细胞的祖细胞。我们模型的一个假设是，每个深层干细胞存在于一个生长抑制微环境中。我们利用文献中的信息建立了一个静止肠道干细胞微环境的模型。据推测，这个微环境主要由一种肠内分泌细胞类型定义，该细胞类型通过分泌生长抑制肽（如生长抑素和鸟苷酸环化酶激活肽/尿鸟苷酸环化酶激活肽）来维持干细胞的静止状态。与该模型一致的是，有证据表明，被假定为定义生长抑制性干细胞微环境的蛋白质可以作为肠道肿瘤抑制因子。证实确实存在生长抑制性微环境将对我们理解肠道稳态和肿瘤发生具有重要意义。
