2011年5月5日,， 我所襲榮文實驗室在 Developmental Biology 雜志上在線發(fā)表題為“EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells”的文章,。該論文報道了果蠅腸上皮干細胞新的調(diào)節(jié)機制，并進一步證明了環(huán)形肌作為微環(huán)境維系干細胞的重要作用,。
成體干細胞通常存在于一個特殊的微環(huán)境中得以長期維持。在果蠅的腸道中,，已知Wnt/Wg 和JAK/STAT信號通路對腸上皮干細胞的維持和更新起重要作用,。它們的信號因子在周圍的環(huán)形肌中分泌，以旁分泌的形式調(diào)節(jié)干細胞的活性,。因此環(huán)形肌構(gòu)成了腸上皮干細胞的微環(huán)境,。在這篇論文中，作者發(fā)現(xiàn)EGFR信號通路也對腸上皮干細胞的維持和更新起重要作用,，并發(fā)現(xiàn)有三個配體參與,。其中一個配體在環(huán)形肌中特異表達，另外兩個在干細胞中表達,。這樣EGF 信號以旁分泌和自分泌兩種形式維持著干細胞的自我更新,。在干細胞中抑制EGFR會引起干細胞的活性下降和丟失。同時抑制三個信號通路可以加重這一表型,，使干細胞在短期內(nèi)完全丟失,。另外，在三個信號通路中,，一個通路的失活導致的干細胞活性下降可以被另外兩個通路的過激活部分代償,。這些結(jié)果表明這三條信號通路共同起作用維持著腸上皮干細胞的自我更新。在人的腸道腫瘤中也常見EGFR通路的激活突變,，因此該論文不但進一步揭示了腸上皮干細胞自我更新的分子機制,，也將有助于理解腸道腫瘤等疾病的發(fā)生機制。
徐娜（博士后）為該論文的第一作者,。其他作者還有王思淇,，譚丹，高亞威,，林國南,。襲榮文博士為本文通訊作者。此項研究為科技部863和北京市科委資助課題,，在北京生命科學研究所完成,。（生物谷Bioon.com）
生物谷推薦原文出處：
Developmental Biology DOI： 10.1016/j.ydbio.2011.03.018
EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells
Na Xua, Si Qi Wanga, Dan Tana, Yawei Gaoa, Guonan Lina and Rongwen Xi, a,
Tissue-specific adult stem cells are commonly associated with local niche for their maintenance and function. In the adult Drosophila midgut, the surrounding visceral muscle maintains intestinal stem cells (ISCs) by stimulating Wingless (Wg) and JAK/STAT pathway activities, whereas cytokine production in mature enterocytes also induces ISC division and epithelial regeneration, especially in response to stress. Here we show that EGFR/Ras/ERK signaling is another important participant in promoting ISC maintenance and division in healthy intestine. The EGFR ligand Vein is specifically expressed in muscle cells and is important for ISC maintenance and proliferation. Two additional EGFR ligands, Spitz and Keren, function redundantly as possible autocrine signals to promote ISC maintenance and proliferation. Notably, over-activated EGFR signaling could partially replace Wg or JAK/STAT signaling for ISC maintenance and division, and vice versa. Moreover, although disrupting any single one of the three signaling pathways shows mild and progressive ISC loss over time, simultaneous disruption of them all leads to rapid and complete ISC elimination. Taken together, our data suggest that Drosophila midgut ISCs are maintained cooperatively by multiple signaling pathway activities and reinforce the notion that visceral muscle is a critical component of the ISC niche.
