细胞分化与重编程过程中DNA甲基化模式异质性研究

项目名称： 细胞分化与重编程过程中DNA甲基化模式异质性研究

项目编号： No.31201002

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 邵小健

作者单位： 滨州学院

项目金额： 25万元

中文摘要： DNA甲基化修饰在干细胞分化和体细胞重编程过程中起着至关重要的作用。在这些过程中伴随着DNA甲基化状态的改变。前人的研究工作多局限于揭示"细胞群体"内DNA甲基化平均水平的变化，还鲜有从细胞个体之间的差异性（即细胞异质性）角度出发的研究工作。随着高通量测序数据的不断涌现，已迫切需要发展新的分析方法从全基因组水平阐释细胞群体异质性的表观遗传机制。为此，本项目拟采用DNA甲基化模式分析新方法度量细胞群体异质性，结合生物信息学技术进行细胞分化和重编程过程中细胞群体的异质性的动态比较，主要是研究DNA甲基化模式在单个细胞群体内基因组不同区域之间的分布，以及其在各个细胞系间的维系与动态变化等问题，并找出与细胞群体异质性相关的关键的表观遗传标识物。本项目的研究不仅可以为生物学家研究细胞分化和重编程过程中DNA甲基化修饰的生物学功能和表观遗传机理提供新的认识，而且可以丰富DNA甲基化模式的分析方法。

中文关键词： 生物信息学；DNA甲基化模式；重编程；细胞异质性；细胞系特异性

英文摘要： DNA methylation plays a key role during stem cell differentiation and somatic cell reprogramming. Numerous efforts have been taken to decipher the epigenetic changes governing these biological processes. With the development of next generation sequencing technologies, large amount of epigenomic sequencing data accumulated rapidly in the past years. More sophisticate tools are highly desired to better understand the methylation information embeded within these large-scale sequencing data. However, the vast majority of previous studies focused on the analysis of methyaltion changes based on the average DNA methylation level. In this study, besides DNA methylation level, we propose to analyze DNA methylation patterns to uncover the heterogeneity of a cell population. More specifically, we are going to evaluate the variations in DNA methylation patterns on genome-wide scale. We aim to assess DNA methylation variations for a large number of genomic loci in different cell populations, including stem cells, iPSCs and differentiated cells. In particular, we will study the DNA methylation patterns of different genomic loci within each cell population, and monitor the dynamic changes in DNA methylation patterns during cell differentiation and cell reprogramming. Our research will generate novel knowledge to understand the

英文关键词： Bioinformatics；DNA methylation pattern；reprogramming；Cell heterogeneity；cell-type specific