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小生境微环境中多梳蛋白和三胸蛋白家族基因对生殖系干细胞分化的调控

Control of germline stem cell differentiation by Polycomb and Trithorax group genes in the niche microenvironment.

作者信息

Li Xuewen, Yang Fu, Chen Hongyan, Deng Bowen, Li Xinghua, Xi Rongwen

机构信息

College of Biological Sciences, China Agricultural University, Beijing 100193, China National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.

National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.

出版信息

Development. 2016 Oct 1;143(19):3449-3458. doi: 10.1242/dev.137638. Epub 2016 Aug 10.

Abstract

Polycomb and Trithorax group (PcG and TrxG) genes function to regulate gene transcription by maintaining a repressive or active chromatin state, respectively. This antagonistic activity is important for body patterning during embryonic development, but whether this function module has a role in adult tissues is unclear. Here, we report that in the Drosophila ovary, disruption of the Polycomb repressive complex 1 (PRC1), specifically in the supporting escort cells, causes blockage of cystoblast differentiation and germline stem cell-like tumor formation. Tumors are caused by derepression of decapentaplegic (dpp), which prevents cystoblast differentiation. Interestingly, activation of dpp in escort cells requires the function of the TrxG gene brahma (brm), suggesting that loss of PRC1 in escort cells causes Brm-dependent dpp expression. Our study suggests a requirement for balanced activity between PcG and TrxG in an adult stem cell niche, and disruption of this balance could lead to the loss of tissue homeostasis and tumorigenesis.

摘要

多梳蛋白和三胸节复合物(PcG和TrxG)基因分别通过维持抑制性或活性染色质状态来调节基因转录。这种拮抗活性对胚胎发育过程中的身体模式形成很重要,但该功能模块在成体组织中是否起作用尚不清楚。在这里,我们报告在果蝇卵巢中,多梳蛋白抑制复合物1(PRC1)的破坏,特别是在支持护送细胞中,会导致成囊母细胞分化受阻和类生殖系干细胞肿瘤形成。肿瘤是由脱磷酸化蛋白(dpp)的去抑制引起的,dpp会阻止成囊母细胞分化。有趣的是,护送细胞中dpp的激活需要TrxG基因brahma(brm)的功能,这表明护送细胞中PRC1的缺失会导致依赖Brm的dpp表达。我们的研究表明,成体干细胞微环境中需要PcG和TrxG之间的平衡活性,这种平衡的破坏可能导致组织稳态的丧失和肿瘤发生。

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