检索结果-南通市图书馆

Epigenetic modulations rendering cell-to-cell variability and phenotypic metastability

Journal of Genetics and Genomics 2016年第8期43卷 503-511页

作者： Shawal Spencer Agustina Gugliotta Natascha Godecke Hansjorg Hauser dagmar wirth Model Systems for Infection and Immunity Helmholtz Centre for Infection ResearchBraunschweig 38124Germany Experimental Hematology Hannover Medical SchoolHannover 30625Germany cell culture laboratory faculty of biochemistry and biological sciencesnational university of the littoralSanta Fe 3000Argentina

Tumor cells display phenotypic plasticity and heterogeneity due to genetic and epigenetic variations which limit the predictability of therapeutic interventions. Chromatin modifications can arise stochas- tically but can also be a consequence of environmental influences such as the microenvironment of cancer cells. A better understanding of the impact and dynamics of epigenetic modulation at defined chromosomal sites is required to get access to the underlying mechanisms. We investigated the epige- netic modulations leading to cell-to-cell heterogeneity in a tumor cell line model. To this end, we analyzed expression variance in 80 genetically uniform cell populations having a single-copy reporter randomly integrated in the genorne. Single-cell analysis showed high intraclonal heterogeneity. Epige- netic characterization revealed that expression heterogeneity was accompanied by differential histone marks whereas contribution of DNA methylation could be excluded. Strikingly, some clones revealed a highly dynamic, stochastically altered chromatin state of the transgene cassette which was accompanied with a metastable expression pattern. In contrast, other clones represented a robust chromatin state of the transgene cassette with a stable expression pattern. Together, these results elucidate locus-specific epigenetic modulation in gene expression that contributes to phenotypic heterogeneity of cells and might account for cellular plasticity.

关键词： lntraclonal heterogeneityEpigenetic regulationDNA methylationDifferential histone marksMetastable expression

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Effective intrahepatic CD8＋ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes

引用

Cellular & Molecular Immunology 2016年第6期13卷 805-815页

作者： Aaron Ochel Marcin Cebula Mathias Riehn Upneet Hillebrand Christoph Lipps Reinhold Schirmbeck Hansjorg Hauser dagmar wirth Model Systems for Infection and Immunity Helmholtz Centre for Infection Research Inhoffenstr. 7 38124 Braunschweig Germany Clinic for Internal Medicine I University Hospital UIm Albert-Einstein-Allee 23 89081 UIm Germany Experimental Hematology Medical School Hannover Carl-Neuberg-Str. 1 D-30625 Hannover Germany Current address Institute for Immunology Justus-Liebig University Giessen BFS Schubertstr. 81 35390 Giessen Germany

Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8＋ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8＋ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin （Ova） as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.

关键词： antigen load chronicity immune modulation T-cell exhaustion

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：