成体干细胞通常利用粘附机制附着在一个特殊的微环境中得以长期维持。果蝇的肠上皮干细胞位于肠上皮的基地部位，与周围的环形肌仅有一层基地膜相间隔。环形肌分泌多个信号因子调节干细胞的维持和活性，因而构成了干细胞的微环境。在这篇论文中，作者发现果蝇的肠上皮干细胞通过表达多个整合素因子将自己铆钉在微环境之中。整合素信号通路的激活不仅介导了肠上皮干细胞与基地膜的粘附，而且是干细胞增殖所必须的。整合素的缺失导致干细胞的维持缺陷，也阻断了干细胞的增殖，并有效阻止了肠息肉相关基因APC缺陷导致的上皮增殖和肿瘤发生。该研究因此证明了整合素信号通路对维持果蝇肠上皮干细胞的活性和促进肠道肿瘤的发生的重要作用。该发现有助于进一步理解干细胞与微环境的相互作用原理，也可能对防治肠道肿瘤等疾病有一定的借鉴意义。（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.
