Transgene-associated human growth hormone expression in pancreatic β-cells impairs identification of sex-based gene expression differences.
Transgene-associated human growth hormone expression in pancreatic β-cells impairs identification of sex-based gene expression differences.
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胰腺β细胞中转基因相关的人类生长激素表达损害了基于性别的基因表达差异的识别。
DOI：
10.1152/ajpendo.00229.2018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Magnuson,MarkA
中科院分区：
文献类型：
--
作者：
Stancill,JenniferS;Osipovich,AnnaB;Cartailler,Jean-Philippe;Magnuson,MarkA
荧光蛋白报告基因广泛用于识别和分选鼠胰腺β细胞。在这项研究中，我们比较了使用的MIP-GFP转基因，这表现出异常表达的人生长激素（hGH），与一个新衍生的Ins 2苹果等位基因，缺乏hGH表达的性别特异性基因的表达。与来自Ins 2Apple/+小鼠的β细胞相比，来自MIP-GFP转基因小鼠的β细胞表现出7，733个基因表达的变化，或超过其转录组的一半。为了确定这些差异如何影响一个典型的差异基因表达研究，我们分析了性别对基因表达的影响，使用两个报告线。在含有Ins 2Apple等位基因的雄性和雌性β细胞之间鉴定出657个差异表达基因。雌性β细胞表现出较高的Xist、Tmed 9、Arpc 3、Eml 2和几种胰岛富集转录因子（包括Nkx 2 - 2和Hnf 4a）表达，而雄性β细胞表现出参与细胞周期调控的基因的普遍较高表达。与此形成鲜明对比的是，对含有MIP-GFP转基因的β细胞进行的相同的雄性与雌性比较仅显示了115个差异表达基因，并且对2个差异表达基因列表进行比较仅显示了17个在两种分析中共有的差异表达基因。这些结果表明：1）雄性和雌性β细胞在关键转录因子和细胞周期调节因子的表达方面存在差异; 2）MIP-GFP转基因可能会减弱区分雄性和雌性β细胞的性别特异性差异，从而削弱性别特异性变异的鉴定。
Fluorescent protein reporter genes are widely used to identify and sort murine pancreatic β-cells. In this study, we compared use of theMIP-GFPtransgene, which exhibits aberrant expression of human growth hormone (hGH), with a newly derivedIns2Appleallele that lacks hGH expression on the expression of sex-specific genes. β-Cells fromMIP-GFPtransgenic mice exhibit changes in the expression of 7,733 genes, or greater than half of their transcriptome, compared with β-cells fromIns2Apple/+mice. To determine how these differences might affect a typical differential gene expression study, we analyzed the effect of sex on gene expression using both reporter lines. Six hundred fifty-seven differentially expressed genes were identified between male and female β-cells containing theIns2Appleallele. Female β-cells exhibit higher expression ofXist,Tmed9,Arpc3,Eml2, and several islet-enriched transcription factors, includingNkx2-2andHnf4a, whereas male β-cells exhibited a generally higher expression of genes involved in cell cycle regulation. In marked contrast, the same male vs. female comparison of β-cells containing theMIP-GFPtransgene revealed only 115 differentially expressed genes, and comparison of the 2 lists of differentially expressed genes revealed only 17 that were common to both analyses. These results indicate that1) male and female β-cells differ in their expression of key transcription factors and cell cycle regulators and2) theMIP-GFPtransgene may attenuate sex-specific differences that distinguish male and female β-cells, thereby impairing the identification of sex-specific variations.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
10.5
作者：
Sander, M;Neubuser, A;German, MS
通讯作者：
German, MS
DOI：
10.1073/pnas.0602956103
发表时间：
2006-06-13
影响因子：
11.1
作者：
Le May, Cedric;Chu, Khoi;Mauvais-Jarvis, Franck
通讯作者：
Mauvais-Jarvis, Franck
影响因子：
15.9
作者：
Tiano, Joseph P.;Delghingaro-Augusto, Viviane;Mauvais-Jarvis, Franck
通讯作者：
Mauvais-Jarvis, Franck
影响因子：
29
作者：
Navarro G;Xu W;Jacobson DA;Wicksteed B;Allard C;Zhang G;De Gendt K;Kim SH;Wu H;Zhang H;Verhoeven G;Katzenellenbogen JA;Mauvais-Jarvis F
通讯作者：
Mauvais-Jarvis F