DNA甲基化对骨髓间充质干细胞成骨分化的作用

发布时间：2018-03-31 01:14

本文选题：5-氮胞苷　切入点：间充质干细胞　出处：《浙江大学》2010年硕士论文

【摘要】： 具有多向分化潜能的骨髓间充质干细胞(Mesenchymal stem cells,MSCs)是组织工程良好的细胞种子来源,然而使干细胞高效地向预定的方向分化还是个很大的挑战,这就需要我们充分了解干细胞分化的调节机制。除了传统的转录因子调节,表观遗传修饰也在干细胞分化调控中也起着十分重要的作用,DNA甲基化修饰是表观遗传调控的主要方式之一。本文以MSCs成骨分化为模型,利用DNA甲基化抑制剂——5-氮胞苷研究了DNA甲基化对MSCs成骨分化的影响。在成骨分化诱导前用5-氮胞苷预处理MSCs 24小时,其成骨分化效率明显提高,并伴随着基因组整体水平上DNA甲基化修饰的减少。在单基因水平上,我们又检测了成骨分化重要调控基因Dlx5上甲基化修饰水平的变化,发现5-氮胞苷预处理后,Dlx5基因的“CpGisland shore”处甲基化水平降低。本文充分证明了DNA甲基化修饰在MSCs分化中的作用,为MSCs未来的研究和应用提供了重要依据和方法。
[Abstract]:Bone marrow mesenchymal stem cells (MSCs), which have the potential of multiple differentiation, are good seed sources for tissue engineering. However, it is still a challenge to differentiate the stem cells efficiently in a predetermined direction. This requires us to fully understand the regulatory mechanisms of stem cell differentiation, in addition to traditional transcription factor regulation, Epigenetic modification also plays an important role in the regulation of stem cell differentiation. DNA methylation is one of the main methods of epigenetic regulation. The effect of DNA methylation on MSCs osteogenic differentiation was studied by using 5-azacytidine, a DNA methylation inhibitor. The osteogenic differentiation efficiency was significantly improved after pretreatment of MSCs with 5-azacytidine for 24 hours before osteogenesis induction. At the single gene level, we also detected the change of methylation modification level on Dlx5, an important regulation gene of osteogenic differentiation. It was found that the methylation level at "CpGisland shore" of Dlx5 gene decreased after pretreatment with 5-azacytidine. The role of DNA methylation in MSCs differentiation was fully demonstrated, which provided an important basis and method for the future study and application of MSCs.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R329

【引证文献】