项目名称: 组蛋白赖氨酸甲基化修饰对癌干细胞重编程的作用机制研究
项目编号: No.31460300
项目类型: 地区科学基金项目
立项/批准年度: 2015
项目学科: 生物科学
项目作者: 扈启宽
作者单位: 宁夏医科大学
项目金额: 42万元
中文摘要: 将重编程技术用于肿瘤细胞,使其首先经重编程成为胚胎干细胞样细胞,再重新诱导分化成终末细胞,从而失去其致瘤性和增殖能力。我们在前期研究中发现,组蛋白甲基化修饰对胶质瘤肿瘤干细胞的干性特征保持起着关键的作用,因此推测可能通过将表观遗传修饰与重编程技术结合而使癌细胞重编程回到胚胎干细胞状态,然后再与诱导分化结合使其重新分化为终末细胞,失去其致瘤性。本课题拟对组蛋白赖氨酸甲基化和去甲基化酶在胶质瘤细胞重编程和诱导再分化过程中的变化情况进行研究,并且尝试通过它们替代一个或者几个重编程转录因子,将胶质瘤细胞退回到胚胎样的癌干细胞状态,再通过诱导分化到终末分化阶段,观察组蛋白甲基化修饰在此过程中的各个阶段的表达变化,以及它们所起的作用,对诱导分化和致瘤性的影响等。
中文关键词: 组蛋白脱甲基化酶;癌干细胞;重编程;诱导分化
英文摘要: Cancer cells could be reprogrammed back to the embryonic stem cell-like cells and then be induced to differentiate into the terminal cells, thereby losing its tumorigenicity and proliferation ability. Histone modifications play an important role in this process. It is possible to achieve a complex reprogramming by simply using epigenetically modifications. histone lysine methylation and their methyltransferase or demethylase may play the key role during process. This project intends to demonstrate the expression changes of the histion lysine methyltransferase and demethylase during the reprogramming and differentiation process, and try to replace one or several reprogramming transcription factors in the glioma cells. We also try to observe the expression of histone methylation changes in the various stages of induced differentiation, and the role they played to tumorigenicity so on.
英文关键词: histone demethylase;cancer stem cell;reprogramming;differentiation