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Liver-specific matrin-3 knockout alters the hepatic transcriptome of chow diet-fed mice [RNA-seq]

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Matrin-3 is an RNA-binding protein involved in the pathogenesis of human diseases. Here we examined the hepatic transcriptome of chow-diet fed mice. Bulk RNA-seq and bioinformatics analysis identified 646 and 145 differentially expressed genes (Padj < 0.05), respectively in the livers of female and male matrin-3 LKO mice. Enrichr analysis of these DEGs revealed several common Hallmark terms including cholesterol homeostasis, fatty acid metabolism, xenobiotic metabolism, and epithelial mesenchymal transition between female and male mice. Our data demonstrated that liver-specific matrin-3 deficiency re-programs the hepatic transcriptome in the liver of chow diet-fed mice. Matrin-3 floxed mice were bred with Albumin-Cre mice (The Jackson Laboratory, #003574) to produce liver-specific matrin-3 knockout mice (LKO). Mice were housed on a normal 12/12 light-dark cycle. Mice had ad libitum access to a normal chow diet (Envigo, cat# 2016) and water. At 16 weeks of age, mice were euthanized for tissue collection. Total RNAs were extracted from mouse tissues after homogenization using TRIzol Reagent (Thermo Fisher, 15596026) according to the manufacturers instructions. For RNA sequencing by Novogene, total RNA quality was examined using Agilent 2100 Bioanalyzer. The RNA Integrity Number of each RNA sample is above 8.5. A total amount of 1 g RNA per sample was used for library construction. Total eight libraries were constructed; one library was produced from two liver tissues; and each group of mice has two library replicates.

Matrin-3是一种参与人类疾病发病机制的RNA结合蛋白。本研究对普通饲料喂养小鼠的肝脏转录组进行了检测。通过批量RNA测序(bulk RNA-seq)和生物信息学分析,分别在雌性和雄性matrin-3肝脏特异性敲除(LKO)小鼠的肝脏中鉴定出646个和145个差异表达基因(Padj < 0.05)。对这些差异表达基因(differentially expressed genes, DEGs)的Enrichr富集分析显示,雌雄小鼠间存在多个共有的特征基因集(Hallmark terms),包括胆固醇稳态、脂肪酸代谢、异生物质代谢以及上皮间质转化。本研究数据表明,肝脏特异性matrin-3缺陷会重塑普通饲料喂养小鼠的肝脏转录组。将Matrin-3 floxed小鼠与白蛋白-Cre(Albumin-Cre)小鼠(The Jackson Laboratory,#003574)杂交,获得肝脏特异性matrin-3敲除小鼠(LKO)。小鼠饲养于12小时光照/12小时黑暗的标准光周期环境中,可自由采食普通饲料(Envigo,cat# 2016)并饮用清水。在小鼠16周龄时,实施安乐死并收集组织样本。按照制造商说明书,使用TRIzol试剂(Thermo Fisher,15596026)对小鼠组织进行匀浆处理,随后提取总RNA。在诺禾致源(Novogene)开展RNA测序前,使用安捷伦2100生物分析仪(Agilent 2100 Bioanalyzer)检测总RNA质量,所有样本的RNA完整性指数均高于8.5。每个样本取1 μg总RNA用于文库构建。共构建8个文库:其中1个文库由2份肝脏组织混合制备,其余每组小鼠设置2个文库重复。

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