2010年5月1日,，NIBS襲榮文實(shí)驗(yàn)室在Genes & Development雜志上發(fā)表題為“Polycomb group genes Psc and Su(z)2 restrict follicle stem cell self-renewal and extrusion by controlling canonical and non-canonical Wnt signaling”的文章,。該文章揭示了多梳基因調(diào)控干細(xì)胞的一個(gè)新的模式和機(jī)制,。
多梳基因家族這一類表觀沉默因子一直被認(rèn)為是維持干細(xì)胞多能性的重要機(jī)制,。它們直接作用于許多與細(xì)胞分化相關(guān)的基因上,，抑制它們的表達(dá),，從而維持干細(xì)胞的未分化狀態(tài),。在這篇論文中，研究人員報(bào)道一些多梳基因在果蠅的上皮干細(xì)胞內(nèi)起恰恰相反的作用,。失去這些基因功能的干細(xì)胞無(wú)法進(jìn)行分化，但不斷進(jìn)行自我繁殖,，從而導(dǎo)致腫瘤的發(fā)生。另外,，突變的干細(xì)胞從基地膜一側(cè)逐漸突出并脫離出上皮層，在異位不斷增長(zhǎng),，形成團(tuán)狀腫瘤組織,。進(jìn)一步的機(jī)制研究發(fā)現(xiàn)干細(xì)胞從基地膜一側(cè)的突出是由非經(jīng)典的Wnt通路介導(dǎo)的,，而腫瘤的形成主要是由于經(jīng)典Wnt通路的持續(xù)激活促使的,。
本論文因此揭示了多梳基因調(diào)控干細(xì)胞的一個(gè)新的模式,，這對(duì)理解干細(xì)胞生物學(xué)的表觀遺傳機(jī)制有重要意義。本論文也揭示了致瘤細(xì)胞發(fā)生轉(zhuǎn)移的一個(gè)新的模式和機(jī)制,，這對(duì)理解腫瘤的發(fā)生和轉(zhuǎn)移機(jī)制有重要的提示作用,，并為進(jìn)一步研究經(jīng)典和非經(jīng)典的Wnt信號(hào)通路在腫瘤形成的作用提供了基礎(chǔ)。
李興華技術(shù)員為該論文的第一作者,。其他作者還有韓月技術(shù)員,，襲榮文博士為論文通訊作者。此項(xiàng)研究為科技部和北京市科委資助課題,，在北京生命科學(xué)研究所完成,。（生物谷Bioon.com）
生物谷推薦原文出處：
Genes&Development doi：10.1101/gad.1901510
Polycomb group genes Psc and Su(z)2 restrict follicle stem cell self-renewal and extrusion by controlling canonical and noncanonical Wnt signaling
Xinghua Li, Yue Han and Rongwen Xi1
National Institute of Biological Sciences, Beijing 102206, People's Republic of China
Stem cells are critical for maintaining tissue homeostasis and are commonly governed by their niche microenvironment, although the intrinsic mechanisms controlling their multipotency are poorly understood. Polycomb group (PcG) genes are epigenetic silencers, and have emerged recently as important players in maintaining stem cell multipotency by preventing the initiation of differentiation programs. Here we describe an unexpected role of specific PcG genes in allowing adult stem cell differentiation and preventing stem cell-derived tumor development. We show that Posterior sex combs (Psc), which encodes a core Polycomb-repressive complex 1 (PRC1) component, functions redundantly with a similar gene, Suppressor of zeste two [Su(z)2], to restrict follicle stem cell (FSC) self-renewal in the Drosophila ovary. FSCs carrying deletion mutations of both genes extrude basally from the epithelium and continue to self-propagate at ectopic sites, leading to the development of FSC-like tumors. Furthermore, we show that the propagation of the mutant cells is driven by sustained activation of the canonical Wnt signaling pathway, which is essential for FSC self-renewal, whereas the epithelial extrusion is mediated through the planar cell polarity pathway. This study reveals a novel mechanism of epithelial extrusion, and indicates a novel role of polycomb function in allowing adult stem cell differentiation by antagonizing self-renewal programs. Given evolutionary conservation of PcG genes from Drosophila to mammals, they could have similar functions in mammalian stem cells and cancer.
