小鼠纹状体与视网膜的比较转录组学分析

Comparative transcriptomic analysis of mouse striatum and retina

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,r RNA)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2478个.其中,1579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 C57 BL/6 mice striatum and retinaribonucleic acid,library was constructed using ribosomal ribonucleic acid(r RNA)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 of2478 genes had significantly different expressions,among which 1579 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.