成體干細(xì)胞通常利用粘附機(jī)制附著在一個特殊的微環(huán)境中得以長期維持,。果蠅的腸上皮干細(xì)胞位于腸上皮的基地部位，與周圍的環(huán)形肌僅有一層基地膜相間隔,。環(huán)形肌分泌多個信號因子調(diào)節(jié)干細(xì)胞的維持和活性,，因而構(gòu)成了干細(xì)胞的微環(huán)境,。在這篇論文中，作者發(fā)現(xiàn)果蠅的腸上皮干細(xì)胞通過表達(dá)多個整合素因子將自己鉚釘在微環(huán)境之中,。整合素信號通路的激活不僅介導(dǎo)了腸上皮干細(xì)胞與基地膜的粘附,，而且是干細(xì)胞增殖所必須的。整合素的缺失導(dǎo)致干細(xì)胞的維持缺陷,，也阻斷了干細(xì)胞的增殖,，并有效阻止了腸息肉相關(guān)基因APC缺陷導(dǎo)致的上皮增殖和腫瘤發(fā)生。該研究因此證明了整合素信號通路對維持果蠅腸上皮干細(xì)胞的活性和促進(jìn)腸道腫瘤的發(fā)生的重要作用,。該發(fā)現(xiàn)有助于進(jìn)一步理解干細(xì)胞與微環(huán)境的相互作用原理,，也可能對防治腸道腫瘤等疾病有一定的借鑒意義。（生物谷Bioon.com）
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Integrin signaling is required for maintenance and proliferation of intestinal stem cells in Drosophila
Guonan Lin, Xi Zhang, Juan Ren, Zhimin Pang, Chenhui Wang, Na Xu, Rongwen Xi
Tissue-specific stem cells are maintained by both local secreted signals and cell adhesion molecules that position the stem cells in the niche microenvironment. In the Drosophila midgut, multipotent intestinal stem cells (ISCs) are located basally along a thin layer of basement membrane that composed of extracellular matrix (ECM), which separates ISCs from the surrounding visceral musculature: the muscle cells constitute a regulatory niche for ISCs by producing multiple secreted signals that directly regulate ISC maintenance and proliferation. Here we show that integrin-mediated cell adhesion, which connects the ECM and intracellular cytoskeleton, is required for ISC anchorage to the basement membrane. Specifically, the α-integrin subunits including αPS1 encoded by mew and αPS3 encoded by scb, and the β-integrin subunit encoded by mys are richly expressed in ISCs and are required for the maintenance, rather than their survival or multiple lineage differentiation. Furthermore, ISC maintenance also requires the intercellular and intracellular integrin signaling components including Talin, Integrin-linked kinase (Ilk), and the ligand, Laminin A. Notably, integrin mutant ISCs are also less proliferative, and genetic interaction studies suggest that proper integrin signaling is a pre-requisite for ISC proliferation in response to various proliferative signals and for the initiation of intestinal hyperplasia after loss of adenomatous polyposis coli (Apc). Our studies suggest that integrin not only functions to anchor ISCs to the basement membrane, but also serves as an essential element for ISC proliferation during normal homeostasis and in response to oncogenic mutations.
