围绕肠壁的环形肌一个众所周知的功能就是产生肠蠕动，促进食物的推进。而在果蝇体内，它还有一个极为重要的功能，那就是维持肠上皮干细胞的自我更新。这项干细胞研究的最新发现由北京生命科学研究所袭荣文博士带领的课题组完成，并在线刊登在9月21日的《自然》（Nature）杂志上。
袭荣文利用果蝇作为实验模型，在分子和细胞水平上证明了干细胞的微环境对干细胞的调控作用。“环形肌构成了肠上皮干细胞的微环境。”他发现，环形肌分泌的信号因子维持着肠上皮干细胞的存在并控制着它的活性。
他说，这种控制着果蝇肠上皮干细胞自我更新的叫做Wnt信号因子，能够穿越一薄层由细胞外基质组成的基底膜，然后到达干细胞的表面，结合并激活干细胞膜上的受体，随之激活一系列下游成员和转录因子，从而在转录水平上调控基因的表达和干细胞的自我更新。抑制Wnt信号通路上任何一个环节都会导致干细胞的分化和丢失。相反，Wnt信号通路的过量激活可以直接导致干细胞的积聚和肿瘤的发生。Wnt信号通路在哺乳动物和人身上也被认为是控制肠上皮干细胞自我更新的一个主要机制。
此项发现证明了以果蝇作为一个模式来解析肠道干细胞调控机制的可行性。果蝇在遗传学上的优势将有助于进一步解析肠道干细胞的调节机制及肠道肿瘤等疾病的发生机制。另外，该研究也揭示了一个崭新的干细胞微环境结构。环形肌作为微环境细胞并不与肠上皮干细胞直接接触，而是被一层基底膜隔开。干细胞散布在基底膜上，并没有局部区域的聚集。研究干细胞的调控机制，对理解肿瘤等疾病的发生进而有针对性地制定干预措施，以期达到治愈目的具有重要意义。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature，doi:10.1038/nature07329，Guonan Lin，Rongwen Xi
Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells
Guonan Lin1,2, Na Xu2 & Rongwen Xi2
1 Graduate program, Peking union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
2 National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
In the Drosophila midgut, multipotent intestinal stem cells (ISCs) that are scattered along the epithelial basement membrane maintain tissue homeostasis by their ability to steadily produce daughters that differentiate into either enterocytes or enteroendocrine cells, depending on the levels of Notch activity1, 2, 3. However, the mechanisms controlling ISC self-renewal remain elusive. Here we show that a canonical Wnt signalling pathway controls ISC self-renewal. The ligand Wingless (Wg) is specifically expressed in the circular muscles next to ISCs, separated by a thin layer of basement membrane. Reduced function of wg causes ISC quiescence and differentiation, whereas wg overexpression produces excessive ISC-like cells that express high levels of the Notch ligand, Delta. Clonal analysis shows that the main downstream components of the Wg pathway, including Frizzled, Dishevelled and Armadillo, are autonomously required for ISC self-renewal. Furthermore, epistatic analysis suggests that Notch acts downstream of the Wg pathway and a hierarchy of Wg/Notch signalling pathways controls the balance between self-renewal and differentiation of ISCs. These data suggest that the underlying circular muscle constitutes the ISC niche, which produce Wg signals that act directly on ISCs to promote ISC self-renewal. This study demonstrates markedly conserved mechanisms regulating ISCs from Drosophila to mammals. The identification of the Drosophila ISC niche and the principal self-renewal signal will facilitate further understanding of intestinal homeostasis control and tumorigenesis.
