苯对C3H/He小鼠骨髓细胞转录组表达的影响:基于转录组测序技术  

Effects of benzene on transcriptome expression of bone marrow cells in C3H/He mice: Based on RNA sequencing technique

作　　者：曹萌[1] 孙凤梅[1] 尹立红[1] 浦跃朴[1] 张娟[1] 

机构地区：[1]东南大学公共卫生学院,环境医学工程教育部重点实验室,江苏南京210009

出　　处：《环境与职业医学》2017年第7期577-585,共9页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金项目(编号:81373034)

摘　　要：[目的]应用转录组测序(RNA sequencing,RNA-seq)技术,研究苯对小鼠骨髓细胞转录组表达和信号通路的影响,为苯对小鼠骨髓细胞毒性的可能作用机制提供科学线索。[方法]将C3H/He小鼠随机分为苯暴露组[160 mg/(kg·d)]与对照组[0 mg/(kg·d)],每组10只,以皮下注射的方式染毒,每周5次,连续4周。分离小鼠的骨髓细胞,应用RNA-seq技术对苯暴露和对照组小鼠的骨髓细胞进行转录组测序,并对测序结果进行基因差异表达、基因功能与信号通路富集以及基因共表达分析。[结果]RNA-seq结果显示,苯染毒后共有227个基因的表达发生明显变化,其中122个基因下调,105个基因上调。基因功能与信号通路富集分析结果显示,这些差异基因主要富集在免疫、凋亡、代谢、氧化应激、造血谱系等功能和通路上。差异基因共表达分析显示,调控度大于10的基因有14个,其中Ccr9、Xaf1、Flt3、Cd72分别是细胞免疫、细胞凋亡、造血细胞谱系、造血细胞分化等通路上的重要基因。[结论]苯暴露可导致小鼠骨髓细胞基因表达谱发生变化,可引起小鼠骨髓细胞免疫、凋亡、代谢、氧化应激、造血谱系等功能与通路发生变化,其中Ccr9、Xaf1、Flt3、Cd72可能起关键性调控作用。[ Objective ] To evaluate the effects of benzene on genes and signal pathways of mouse bone marrow cells using RNA sequencing （RNA-seq）, and to provide novel clues for studying potential mechanism of benzene toxicity to bone marrow cells. [ Methods ] C3H/He mice were randomly divided into two groups with ten mice each： control [0mg/（kg.d）] and benzene exposure [160 mg/（kg-d）] groups. Mice were injected subcutaneously five times per week for four weeks. The separated bone marrow cells were sequenced by RNA-seq technique, and the gene differential expression, enrichment of gene function and signal pathway, and gene co-expression were analyzed. [ Results ] The RNA-seq results showed that there were 227 genes differently expressed after the designed benzene exposure, of which 122 genes were down-regulated and 105 genes were up-regulated. The enrichment analysis results of gene function and signal pathway showed that these differential genes were mainly enriched in immunization, apoptosis, metabolism, oxidative stress, and hematopoietic cell lineage related functions and pathways. The results of gene co-expression analysis showed that there were 14 genes with regulation degrees greater than 10, in which Ccr9, Xafl, Flt3, and Cd72 were critical genes involved in immunization,apoptosis, hematopoietic cell lineage, and hematopoietic cell differentiation, respectively. [ Conclusion ] Benzene exposure could induce altered transcriptome expression in bone marrow cells in mice and affect immunization, apoptosis, metabolic process, oxidative stress, and hematopoietic cell lineage related functions and pathways. Ccr9, Xafl, Flt3, and Cd72 might play a key regulatory role in benzene induced hematopoietic toxicity.

关 键 词：苯 RNA-SEQ 骨髓细胞 差异表达 信号通路 

分 类 号：R114[医药卫生—卫生毒理学]