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预测 miRNA-mRNA 介导的转录后调控与颈胸胸腺功能差异相关。

Predicted miRNA-mRNA-mediated posttranscriptional control associated with differences in cervical and thoracic thymus function.

机构信息

Molecular Immunogenetics Group, Department of Genetics, Ribeirão Preto Medical School, University of São Paulo (USP), 14049-900, Ribeirão Preto, São Paulo, Brazil.

Department of Genetics, University of Georgia, Athens, GA, 30602, USA.

出版信息

Mol Immunol. 2018 Jul;99:39-52. doi: 10.1016/j.molimm.2018.04.003. Epub 2018 May 26.

Abstract

A secondary cervical thymus (CT) is present in the neck region in about 50% of human and mice. CT in mice is an independent and functional organ, which can be colonized by T lymphocyte progenitors and generate thymocytes that are selected by the T cell receptor repertoire following the positive and negative selection. However, CT and the main thoracic thymus (TT) have been shown in mice to have significant functional differences. In this study, we use transcriptional profiling to compare mRNA or miRNAs expression patterns in murine CT and TT. We used these data to perform functional enrichment of the expression signatures and reconstruction of posttranscriptional miRNA-mRNA interaction networks. For this purpose, we compared the transcriptome profiling of paired RNA samples of whole CTs, TTs and parathyroid gland (PT), which was used as an external group, from Foxn1-GFP;Pth-Cre;R26dTomato transgenic mice that differentially label CT and TT. As expected, CT and TT featured comprehensive transcriptome similarity and this suggests that these organs are subjected to correlated transcriptional control. Nevertheless, significant differences were also observed between TT and CT, characterized by 107 differentially expressed (DE) mRNAs, and in 13 DE miRNAs, that in turn established interactions. These results suggest that functional similarity between TT and CT is reflected in their transcriptional activity and that CT functional uniqueness might be under posttranscriptional control.

摘要

一个次要的颈部胸腺(CT)在约 50%的人类和老鼠的颈部区域存在。CT 在老鼠中是一个独立的和功能器官,可以被 T 淋巴细胞前体定植,并产生胸腺细胞,这些细胞在 T 细胞受体库的正选择和负选择后被选择。然而,已经表明 CT 和主要的胸胸腺(TT)在老鼠中有显著的功能差异。在这项研究中,我们使用转录谱分析比较了小鼠 CT 和 TT 的 mRNA 或 miRNA 表达模式。我们使用这些数据对表达特征进行了功能富集,并重建了转录后 miRNA-mRNA 相互作用网络。为此,我们比较了来自 Foxn1-GFP;Pth-Cre;R26dTomato 转基因小鼠的整个 CT、TT 和甲状旁腺(PT)的配对 RNA 样本的转录组谱,这些小鼠差异标记 CT 和 TT。正如预期的那样,CT 和 TT 具有全面的转录组相似性,这表明这些器官受到相关的转录控制。然而,TT 和 CT 之间也观察到了显著的差异,表现为 107 个差异表达(DE)mRNA 和 13 个 DE miRNAs,这些差异反过来又建立了相互作用。这些结果表明,TT 和 CT 之间的功能相似性反映在它们的转录活性上,而 CT 的功能独特性可能受到转录后控制。

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