深圳大学学报理工版

已发现以纹状体多巴胺减少为主要病变之一的帕金森综合症(Parkinson's disease, PD),可能伴有视网膜病理改变.通过分析比较小鼠纹状体及视网膜在转录组水平的基因表达谱异同,探讨PD相关视网膜病理改变的潜在分子基础.对正常成年C57BL/6小鼠的纹状体和视网膜进行核糖体核糖核酸(ribosomal ribonucleic acid, rRNA)减除法建库、转录组测序和生物信息学分析,比较两者基因表达谱的异同,分析差异基因所富集的基因功能和信号通路. 重点比较两者PD信号通路基因表达的异同,并构建相关基因互作网络.比较转录组学分析发现两者显著差异表达的基因共2 478个.其中,1 579个基因在纹状体中呈高表达; 899个基因在视网膜中呈高表达.在纹状体中,高表达基因富集的功能和通路主要与信号转导及膜转运相关; 而在视网膜中,则表现为与转录和光转导相关.PD信号通路有11个基因在纹状体高表达,而在视网膜呈现显著低表达,该通路中其他大多数基因则在两种组织间有相似的表达模式.研究结果揭示了小鼠纹状体和视网膜在转录组水平上的基因表达谱的异同,并探索了与PD相关视网膜病变的潜在分子基础.

Parkinson's disease(PD), with decreased dopamine in the striatum as one of the major lesions, may be accompanied by retinopathy. By analyzing and comparing the gene expression patterns in the mouse striatum and retina at the transcriptome level, the potential molecular basis of PD-related retinopathy was explored. From normal adult C57BL/6 mice striatum and retinaribonucleic acid, library was constructed using ribosomal ribonucleic acid(rRNA)depletion, and sequenced on the Illumina Hiseq 4000 platform. After bioinformatic analysis of sequencing data, the expression profiles of the striatum and retina were compared, and differentially expressed genes were identified, followed by gene ontology(GO)and Kyoto encyclopedia of gene and genomes(KEGG)pathway analysis. Andgene networks were constructed from the differentially expressed genes. Results showed that a total of 2 478 genes had significantly different expressions, among which 1 579 and 899 genes were highly expressed in the striatum and retina respectively. GO and KEGG analysis showed that genes highly expressed in the striatum were mainly enriched in signal transduction and membrane transport, while those highly expressed in the retina were associated with transcription and phototransduction. 11 genes in the PD pathway among the highly expressed genes in the striatum, showed significantly lower expression in the retina, while most of the other genes in the pathway had similar expression patterns between the two tissues. Our studythus demonstrated the similarities and differences in gene expression profiles between the mouse striatum and retina, and provided useful evidence tobetter understand the molecular basis of retinopathy in PD.

引言
1 材料与方法
2 结果与分析
3 讨论
4 结语

图1 小鼠脑纹状体与视网膜转录组水平的差异表达热图<br/>Fig.1 (Color online)Differentially expressed genes between mouse striatum and retina

图1 小鼠脑纹状体与视网膜转录组水平的差异表达热图
Fig.1 (Color online)Differentially expressed genes between mouse striatum and retina

图2 小鼠脑纹状体比对视网膜高表达差异基因的GO分析<br/>Fig.2 (Color online)Enriched genes with significantly higher expression in mouse striatum compared with those in the retina by GO analysis

图2 小鼠脑纹状体比对视网膜高表达差异基因的GO分析
Fig.2 (Color online)Enriched genes with significantly higher expression in mouse striatum compared with those in the retina by GO analysis

图3 小鼠脑纹状体比对视网膜低表达差异基因的功能富集分析<br/>Fig.3 (Color online)Enriched genes with significantly lower expression in mouse striatum compared with those in the retina by GO analysis

图3 小鼠脑纹状体比对视网膜低表达差异基因的功能富集分析
Fig.3 (Color online)Enriched genes with significantly lower expression in mouse striatum compared with those in the retina by GO analysis

图4 小鼠脑纹状体比对视网膜高表达差异基因的KEGG通路分析<br/>Fig.4 (Color online)Pathways enriched genes with significantly higher expression in mouse striatum compared with those in the retina by KEGG analysis

图4 小鼠脑纹状体比对视网膜高表达差异基因的KEGG通路分析
Fig.4 (Color online)Pathways enriched genes with significantly higher expression in mouse striatum compared with those in the retina by KEGG analysis

图5 小鼠脑纹状体比对视网膜低表达差异基因的KEGG通路分析<br/>Fig.5 (Color online)Pathways enriched genes with significantly lower expression in mouse striatum compared with those in the retina by KEGG analysis

图5 小鼠脑纹状体比对视网膜低表达差异基因的KEGG通路分析
Fig.5 (Color online)Pathways enriched genes with significantly lower expression in mouse striatum compared with those in the retina by KEGG analysis

图6 利用STRING数据库构建的小鼠脑纹状体相比于视网膜高表达的帕金森病通路的基因互作网络<br/>Fig.6 (Color online)Constructed gene network of PD pathway based on genes with higher expression in mouse striatum compared with retina

图6 利用STRING数据库构建的小鼠脑纹状体相比于视网膜高表达的帕金森病通路的基因互作网络
Fig.6 (Color online)Constructed gene network of PD pathway based on genes with higher expression in mouse striatum compared with retina

图7 在小鼠脑纹状体和视网膜中帕金森通路基因的差异表达比较<br/>Fig.7 Comparison of differentially expressed genes of PD pathway between mouse striatum and retina

图7 在小鼠脑纹状体和视网膜中帕金森通路基因的差异表达比较
Fig.7 Comparison of differentially expressed genes of PD pathway between mouse striatum and retina

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引言

1 材料与方法

2 结果与分析

3 讨论

4 结语

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