Non-random organization of the Biomphalaria glabrata genome in interphase Bge cells and the spatial repositioning of activated genes in cells co-cultured with Schistosoma mansoni

Non-random organization of the Biomphalaria glabrata genome in interphase Bge cells and the spatial repositioning of activated genes in cells co-cultured with Schistosoma mansoni
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DOI:
10.1016/j.ijpara.2010.07.015
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发表时间:
2011-01-01
影响因子:
4
通讯作者:
Bridger, Joanna M.
Bridger, Joanna M.
中科院分区:
医学2区
文献类型:
--
作者:
Knight, Matty;Ittiprasert, Wannaporn;Bridger, Joanna M.

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光秃生物phalaria glabrata是人类血吸虫病病原曼氏血吸虫(Schistosoma mansoni)寄生吸虫的主要中间宿主。为了破译这种宿主-寄生虫相互作用的分子基础,Bge胚胎细胞系提供了一个独特的体外模型系统来评估蜗牛和寄生虫之间的相互作用是否会影响两者的细胞和基因组生物学。利用图像分析技术,通过定位细胞核内不同大小的染色体区域,研究了Bge细胞中光斑叶藻基因组的组织结构。蜗牛的染色体区域在形态和非随机径向定位上与其他衍生的原口和后口生物相似。4个基因位点piwi的特异性监测。BgPrx、肌动蛋白和铁蛋白揭示了基因组的非随机径向定位。这表明蜗牛基因组的特定部分位于可复制的核地址中。为了确定暴露于寄生虫是否反映在基因组组织中,在将Bge细胞与正常或辐照减毒的miracidia共培养30分钟至24小时后,对基因的间期空间定位进行了评估。通过荧光原位杂交(FISH)观察到它们的径向核位置,即它们在间期核中相对于核边缘/包膜的位置。有趣的是,在与正常miracidia共培养的Bge细胞中,大规模的基因重定位与基因表达水平的时间动力学相关,而辐照寄生虫未能引起类似的基因表达或基因位点重定位,使用铁蛋白基因证明了这一点。这表明正常而非减毒的血吸虫提供刺激,引起宿主反应,反映在宿主的核结构中。我们认为,这不仅是第一次在软体动物中进行基因重新定位研究,而且还证明了寄生虫影响其宿主的间期基因组组织。(C) 2010由爱思唯尔有限公司代表澳大利亚寄生虫学学会出版。
Biomphalaria glabrata is a major intermediate host for the parasitic trematode Schistosoma mansoni, a causative agent of human schistosomiasis. To decipher the molecular basis of this host-parasite interaction, the Bge embryonic cell line provides a unique in vitro model system to assess whether interactions between the snail and parasite affect the cell and genome biology in either organism. The organization of the B. glabrata genome in Bge cells was studied using image analysis through positioning territories of differently sized chromosomes within cell nuclei. The snail chromosome territories are similar in morphology as well as in non-random radial positioning as those found in other derived protostome and deuterostome organisms. Specific monitoring of four gene loci, piwi. BgPrx, actin and ferritin, revealed non-random radial positioning of the genome. This indicates that specific parts of the snail genome reside in reproducible nuclear addresses. To determine whether exposure to parasite is reflected in genome organization, the interphase spatial positioning of genes was assessed after co-culturing Bge cells with either normal or irradiation attenuated miracidia for 30 min to 24 h. The loci of actin and ferritin, genes that are up-regulated in the snail when subjected to infection, were visualized by fluorescence in situ hybridisation (FISH) and their radial nuclear positions i.e. their position in the interphase nucleus with respect to the nuclear edge/envelope, mapped. Interestingly, large scale gene repositioning correlated to temporal kinetics of gene expression levels in Bge cells co-cultured with normal miracidia while irradiated parasites failed to elicit similar gene expression or gene loci repositioning as demonstrated using the ferritin gene. This indicates that normal but not attenuated schistosomes provide stimuli that evoke host responses that are reflected in the host's nuclear architecture. We believe that this is not only the first time that gene-repositioning studies have been attempted in a mollusc but also demonstrates a parasite influencing the interphase genome organization of its host. (C) 2010 Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.