2010年5月1日，NIBS袭荣文实验室在Genes & Development杂志上发表题为“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。该文章揭示了多梳基因调控干细胞的一个新的模式和机制。
多梳基因家族这一类表观沉默因子一直被认为是维持干细胞多能性的重要机制。它们直接作用于许多与细胞分化相关的基因上，抑制它们的表达，从而维持干细胞的未分化状态。在这篇论文中，研究人员报道一些多梳基因在果蝇的上皮干细胞内起恰恰相反的作用。失去这些基因功能的干细胞无法进行分化，但不断进行自我繁殖，从而导致肿瘤的发生。另外，突变的干细胞从基地膜一侧逐渐突出并脱离出上皮层，在异位不断增长，形成团状肿瘤组织。进一步的机制研究发现干细胞从基地膜一侧的突出是由非经典的Wnt通路介导的，而肿瘤的形成主要是由于经典Wnt通路的持续激活促使的。
本论文因此揭示了多梳基因调控干细胞的一个新的模式，这对理解干细胞生物学的表观遗传机制有重要意义。本论文也揭示了致瘤细胞发生转移的一个新的模式和机制，这对理解肿瘤的发生和转移机制有重要的提示作用，并为进一步研究经典和非经典的Wnt信号通路在肿瘤形成的作用提供了基础。
李兴华技术员为该论文的第一作者。其他作者还有韩月技术员，袭荣文博士为论文通讯作者。此项研究为科技部和北京市科委资助课题，在北京生命科学研究所完成。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
