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利用多种诱导剂构建的果蝇肠道损伤模型中肠干细胞调控基因的预测:基于差异基因表达的蛋白质-蛋白质相互作用网络分析。

Prediction of intestinal stem cell regulatory genes from Drosophila gut damage model created using multiple inducers: Differential gene expression-based protein-protein interaction network analysis.

机构信息

Department of Integrative Biological Sciences and Industry, Sejong University, Seoul, 05006, South Korea.

Department of Biochemistry, College of Medicine, Dongguk University, Gyeongju, 38766, South Korea.

出版信息

Dev Comp Immunol. 2023 Jan;138:104539. doi: 10.1016/j.dci.2022.104539. Epub 2022 Sep 8.

Abstract

Intestinal tissue functions in innate immunity to prevent the entry of harmful substances, and to maintain homeostasis through the constant proliferation of intestinal stem cells (ISC). To understand the mechanisms which regulate ISC in response to gut damage, we identified 81 differentially expressed genes (DEGs) through RNA-seq analysis after oral administration of three intestinal-damaging substances to Drosophila melanogaster. Through protein-protein interaction (PPI) and functional annotation studies, the top 22 DEGs ordered by the number of nodes in the PPI network were analyzed in relation to cell development. Through network topology analysis, we identified 12 essential seed genes. From this we confirmed that p53, RpL17, Fmr1, Stat92E, CG31343, Cnot4, CG9281, CG8184, Evi5, and to were essential for ISC proliferation during gut damage using knockdown RNAi Drosophila. This study presents a method for identifying candidate genes relating to intestinal damage that has scope for furthering our understanding of gut disease.

摘要

肠道组织在先天免疫中发挥作用,以防止有害物质的进入,并通过肠干细胞(ISC)的不断增殖来维持体内平衡。为了了解调节 ISC 以响应肠道损伤的机制,我们通过 RNA-seq 分析,鉴定了三种肠道损伤物质口服给予果蝇后 81 个差异表达基因(DEGs)。通过蛋白质-蛋白质相互作用(PPI)和功能注释研究,对 PPI 网络中节点数量最多的前 22 个 DEGs 进行了与细胞发育相关的分析。通过网络拓扑分析,我们确定了 12 个必需的种子基因。由此我们证实,p53、RpL17、Fmr1、Stat92E、CG31343、Cnot4、CG9281、CG8184、Evi5 和 to 在肠道损伤时通过敲低 RNAi 果蝇的 ISC 增殖是必需的。本研究提出了一种鉴定与肠道损伤相关的候选基因的方法,有望进一步了解肠道疾病。

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