酵母转录调控协作网络的分析

协作网通常被用于描述各种社会关系,相似的概念也可以应用到转录调控网络的研究中.针对被调控基因共享转录因子的相似性,可以建立一个被调控基因协作网,同样,根据转录因子调控基因的相似性可以建立一个相对较小的转录因子协作网.对被调控基因协作网的聚类研究发现,大部分的类都显著地富集一个或者多个GO功能注释.进一步的结果分析发现某些GO注释的基因更倾向于共享相似的调控机制.这表明,在协作网中,相对简单的调控机制相似性能捕捉生物功能相关的信息.并且,将在二部图分析中使用的概念--"异常点"引入到协作网的分析中,发现协作网的异常点和致死基因有相关性.综上所述,协作网的方法是分析转录调控网络的一个有用的补充.     

脂肪细胞分化相关基因在大鼠再生肝中表达变化

肝脏由多种细胞构成,肝再生与细胞分化密切相关,细胞分化受基因转录水平调控。为在基因转录水平了解脂肪细胞分化基因在大鼠肝再生中作用,本文用搜集网站资料和查阅相关论文等方法获得上述基因,用Rat Genome2302.0芯片检测它们在大鼠肝再生(liver regeneration,LR)中表达情况,将三次检验结果相同或相似、在肝再生中表达变化2倍以上、真手术组和假手术组相比差异显著的基因视为肝再生相关基因。初步证实上述基因中75个基因与肝再生相关。肝再生启动(PH后0.5-4h)、G0/G1过渡(PH后4-6h)、细胞增殖(PH后6-66h)、细胞分化和组织结构功能重建(PH后72-168h)等四个阶段起始表达的基因数为44、13、30和1;基因的总表达次数为88、58、302和90。表明相关基因主要在肝再生启动阶段起始表达,在不同阶段发挥作用。它们共表达上调313次、下调167次,分为43种表达方式。表明肝再生中脂肪细胞发生和分化相关基因活动多样和复杂。根据本文研究结果推测,上述基因不仅调节脂肪细胞分化,而且参与肝再生的生理生化活动。     

Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy

Background

Although 70% (or 2/3) partial hepatectomy (PH) is the most studied model for liver regeneration, the hepatic protein expression profile associated with lower volume liver resection (such as 50% PH) has not yet been reported. Therefore, the aim of this study was to determine the global protein expression profile of the regenerating mouse liver following 50% PH by differential proteomics, and thereby gaining some insights into the hepatic regeneration mechanism(s) under this milder but clinically more relevant condition.

Results

Proteins from sham-operated mouse livers and livers regenerating for 24 h after 50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass spectrometry. Compared to sham-operated group, there were totally 87 differentially expressed proteins (with 50 up-regulated and 37 down-regulated ones) identified in the regenerating mouse livers, most of which have not been previously related to liver regeneration. Remarkably, over 25 differentially expressed proteins were located at mitochondria. Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration. Pathway analysis revealed a central role of c-Myc in the regulation of liver regeneration.

Conclusions

Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.     

Identification of genes specific to “oval cells” in the rat 2-acetylaminofluorene/partial hepatectomy model

Under certain conditions liver regeneration can be accomplished by hepatic progenitor cells (“oval cells”). So far, only few factors have been identified to be uniquely regulated by the “oval cell” compartment. Using macroarray analysis in a rat model of oval cell proliferation (treatment with 2-acetylaminofluorene and partial hepatectomy, AAF + PH), we identified 12 differentially expressed genes compared to appropriate control models (AAF treatment and sham operation or AAF treatment alone). Further analysis in models of normal liver regeneration (ordinary PH) and acute phase response (turpentine oil-treated rats) revealed that three out of 12 genes (thymidine kinase 1, Jun-D and ADP-ribosylation factor 4) were not affected by the hepatic acute phase reaction but similarly overexpressed in both “oval cell”-dependant and normal liver regeneration. We characterized Jun-D and ADP-ribosylation factors as novel factors upregulated in oval cells and in non-parenchymal liver cells of normally regenerating livers. However, two out of 12 differentially expressed genes were specifically expressed in oval cells: ras-related protein Rab-3b and Ear-2. On protein level, Rab-3b was increased in total liver homogenates and demonstrated only in clusters of oval cells. We postulate that Ear-2 and Rab-3b may represent novel regulatory factors specifically activated in “oval cells”.