Rasmussen脑炎患者脑组织的转录组学特征分析

Analysis of transcriptomic characteristics of brain tissue in patients with Rasmussen encephalitis

目的探究Rasmussen脑炎(Rasmussen encephalitis,RE)患者脑组织的转录组学特征。方法采用RNA-seq的方法,对2008年4月至2013年12月首都医科大学附属北京三博脑科医院收治的RE及颞叶癫痫(temporal lobe epilepsy,TLE)患者(对照)中各选取4例脑组织的基因表达谱进行检测。结果聚类分析显示RE患者及对照脑组织差异表达基因(differentially expressed genes,DEGs)谱存在明显差异。共筛选出1285个DEGs,其中782个(60.9%)下调,503个(39.1%)上调。上调表达的DEGs主要富集于神经元信号转导相关的通路,可能与RE患者频繁的癫痫发作相关;下调表达的DEGs主要富集于细胞骨架、细胞周期及趋化作用相关的通路,可能与RE患者脑组织中神经元的丢失及再生以及部分病原体感染后的免疫应答相关。上调表达的关键基因为TAS2R40、HTR4、NAP1L2,下调表达的关键基因为CXXC1、SEPTIN8、CCR7。结论RE患者脑组织的转录组学具有明显特征,DEGs主要富集于神经元信号转导、细胞周期以及趋化作用相关的通路中。

Objective To investigate the transcriptomic characteristics of the brain tissue in patients with Rasmussen encephalitis(RE). Methods RNA-seq technique was used to detect the gene expression profiles in the brain tissues from 4 patients with RE and 4 with temporal lobe epilepsy(TLE) admitted to Sanbo Brain Hospital, Capital Medical University between April, 2008 and December, 2013. Results Cluster analysis showed significant differences in the differentially expressed genes(DEGs) in the brain tissue between the patients with RE and those with TLE. We identified a total of 1 285 DEGs, of which 782(60.9%) were down-regulated and 503(39.1%) were up-regulated in RE. The up-regulated DEGs were mainly enriched in the pathways associated with neuronal signal transduction, possibly in relation with frequent seizures in patients with RE;the down-regulated DEGs were mainly enriched in the pathways associated with cytoskeleton, cell cycle and chemotaxis, which may be related to neuronal loss and regeneration and immune responses to infection by some pathogens in the brain tissue of patients with RE. TAS2 R40, HTR4 and NAP1 L2 were identified as the key up-regulated DEGs, and CXXC1, SEPTIN8 and CCR7 as the key down-regulated DEGs. Conclusion The brain tissue of patients with RE shows characteristic transcriptomic changes, and the DEGs are mainly enriched in neuronal signal transduction, cell cycle and chemotaxis-related pathways.