不同氧体积分数对人胚胎干细胞基因表达谱的影响  

Effects of different oxygen tensions on gene expression profiling of human embryonic stem cells

作　　者：郭丽媛[1,2,3] 刘维强[1,2,3] 何文智[1,2,3] 黎青[1,2,3] 孙筱放[1,2,3] 

机构地区：[1]广州医学院第三附属医院妇产科研究所,广东省广州市510150 [2]广东省产科重大疾病重点实验室,广东省广州市510150 [3]广州市生殖与遗传重点实验室,广东省广州市510150

出　　处：《中国组织工程研究》2012年第49期9168-9173,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(30871378;U1132005);广东省医学科研基金资助项目(A2011280)~~

摘　　要：背景:低氧培养人胚胎干细胞的相关研究主要集中在干细胞多能性的维持及分化方面,而低氧对人胚胎干细胞基因表达水平的影响研究甚少。目的:观察不同氧体积分数对人胚胎干细胞基因表达谱的影响。方法:分别在低氧(体积分数5%O2)和常氧(体积分数21%O2)的条件下持续培养FY-hES-7细胞,收集晚期(第52代)细胞,运用全基因组表达谱芯片技术检测不同氧体积分数组FY-hES-7细胞的基因表达谱,并进行差异基因的功能富集分析及通路分析。结果与结论:与常氧组相比,低氧组表达上调(>2倍)的基因1840个,表达下调(>2倍)的基因1676个。利用基因本体分析发现低氧组表达上调基因与细胞表面受体信号转导、免疫反应、离子转运、生物代谢及细胞活动等功能相关,而表达下调基因则与转录调控,依赖DNA的转录调控、神经分化、细胞形态、胚胎形态、胚胎器官及各系统发育等功能相关。通路分析发现低氧组表达上调的基因与细胞因子受体的相互作用、免疫反应以及造血系统等通路的改变相关,而表达下调的基因则多与胚胎发育及肿瘤通路改变相关。不同氧体积分数下长期培养的人胚胎干细胞基因表达谱存在明显的差异,低氧组出现差异表达基因的功能分析表明低氧有助于人胚胎干细胞的自我更新,防止分化及降低成瘤性。BACKGROUND： The studies describing culture of human embryonic stem cells under hypoxic condition mainly focus on the maintenance of pluripotency and differentiation. There are few studies regarding the effects of hypoxia on gene expression in human embryonic stem cells. OBJECTIVE： To investigate the effects of different oxygen tensions on gene expression profiling of human embryonic stem cells. METHODS： Gene expression profiling determined by Human Gene Expression Microarrays and differentially expressed genes were analyzed by gene ontology and pathway analysis in one human embryonic stem cell line （FY-hES-7） following prolonged passage under hypoxia （5%O2） and normoxia （21%O2）, respectively. RESULTS AND COCLUSlON： 1 840 upregulated genes （more than two folds） and 1676 downregulated genes （more than two folds） were identified in the hypoxic group as compared to the nomorxic group. Gene ontology analysis and pathway analysis showed that gene upregulation in the hypoxic group was associated with cell surface receptor linked signal transduction, immune response, ion transport, metabolic process, cell activation and some pathways such as cytokine-cytokine interaction, immune response, but gene downregulation in the hypoxic group was related to transcription regulation, transcription DNA-dependent regulation, neuronal differentiation, cell morphogenesis, embryonic morphogenesis, embryonic organ and system development and the pathways of embryo development and cancer. The gene expression profiling of human embryonic stem cells in different O2 tensions is variable and the functional analyses of differentially expressed genes in hypoxia are beneficial for human embryonic stem cell culture by keeping stable self-renewal capacity, preventing human embryonic stem cell differentiation and reducing the risk of tumor formation.

关 键 词：低氧 氧体积分数 人胚胎干细胞 表达谱 基因通路 干细胞 

分 类 号：R394.2[医药卫生—医学遗传学]