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人源和猪源脉络丛细胞对 2 型单纯疱疹病毒感染的比较转录组分析提示缺氧的作用

A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Serotype 2 Infection Points to a Role of Hypoxia.

机构信息

Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Institute for Cell Biology, University Hospital Essen, Essen, Germany.

出版信息

Front Cell Infect Microbiol. 2021 Mar 8;11:639620. doi: 10.3389/fcimb.2021.639620. eCollection 2021.

Abstract

() is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs and humans. Previous observations in -infected pigs revealed lesions at the choroid plexus (CP). experiments with primary porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells demonstrated that can invade and traverse the CP epithelium, and that the CP contributes to the inflammatory response cytokine expression. Here, next generation sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and HIBCPP cells challenged with serotype (ST) 2 infected , and of pigs infected . Identified differentially expressed genes (DEGs) were, amongst others, involved in inflammatory responses and hypoxia. The RNA-seq data were validated quantitative PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and in the CP of pigs suffering from ST2 meningitis, respectively, of which eight GSs overlapped between the three different sample sets. The majority of these GSs are involved in cellular signaling and pathways, immune response, and development, including inflammatory response and hypoxia. In contrast, suppressed GSs observed during and ST2 infections included those, which were involved in cellular proliferation and metabolic processes. This study suggests that similar cellular processes occur in infected human and porcine CP epithelial cells, especially in terms of inflammatory response.

摘要

()是一种重要的机会性病原体,可导致猪和人类的败血症和脑膜炎。先前对感染猪的观察发现脉络丛(CP)有病变。用原代猪脉络丛上皮细胞(PCPEC)和人脉络丛上皮乳头瘤(HIBCPP)细胞进行的实验表明,能够侵袭和穿过 CP 上皮细胞,CP 有助于炎症反应和细胞因子表达。在这里,下一代测序(RNA-seq)用于比较受 ST2 感染的 PCPEC 和 HIBCPP 细胞以及感染猪的 CP 中受挑战的细胞的全转录组谱。鉴定的差异表达基因(DEGs)除其他外,还参与炎症反应和缺氧。RNA-seq 数据通过对选定 DEGs 的定量 PCR 进行了验证。采用基因集富集分析(GSEA),分别鉴定了感染 HIBCPP 细胞、PCPEC 和感染 ST2 脑膜炎猪 CP 的 18、28 和 21 个富集特征基因集(GSs),其中 8 个 GSs 在三个不同样本集中重叠。这些 GSs 的大多数涉及细胞信号转导和途径、免疫反应和发育,包括炎症反应和缺氧。相比之下,在 和 ST2 感染期间观察到的受抑制的 GSs 包括那些涉及细胞增殖和代谢过程的 GSs。这项研究表明,受感染的人源和猪源 CP 上皮细胞中发生了类似的细胞过程,尤其是在炎症反应方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/7982935/8ae573ba6911/fcimb-11-639620-g001.jpg

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