LaminA对小鼠体胞重编程及ES分化的作用分析.docxVIP

Abstract摘要 Abstract 摘要 自从2006年Takahashi和Yamanaka报道成功建立小鼠的诱导多能性干细胞 以来，全世界众多实验室开始了iPS细胞研究，并取得了巨大进展。体细胞重编 程是一个复杂的过程，具体机制目前还不清楚。众多科学家对如何提高ips形成 效率和获得质量及安全性做出了大量的实验工作，最近Shinya Yamanaka、Konrad Hochedlinger等人发现抑$IJP53在人成体细胞或小鼠胎儿成纤维细胞中的表达 能大大提高ips的产生效率。最新研究表明；A型核纤层蛋白均对端粒的结构， 长度和功能维持的关键作用，另外其可稳定DNA损伤反应(DDR)途径中重要组 分一P53。一些科学家对胚胎形成期核纤层蛋白表达与细胞分化之间的关系进 行了研究，结果表明细胞在不同分化发育阶段，不同的核纤层蛋白表达程度不尽 相同。低水平核纤层蛋白A是细胞核处于组织结构程度较低的细胞特征，使得细 胞具有更好的分化增殖潜能，因此低lamina可能使细胞比较容易逆转到未分化 状态． 我们成功从C57d、鼠获取关键的实验材料，并采用pSIREN-RetroQ RNA干扰 及稳定型过表达体系pCMV—Ta92，详细探讨了laminA在体细胞重编程过程中以及 在ES细胞多能性维持和分化中的作用和特点，我们结果表明lamina的表达量不 仅与细胞分化程度和衰老程度有密切关系，除此之外，我们发现laminA的降低 或沉默对体细胞重编程效率的提高是必须的，同样lamina对ES细胞多能性及自 我更新功能的维持也具有重要作用。 关键词：lamina体细胞重编程ES ips分化多能性端粒酶 V AbstractA Abstract A bstract Since Takahashi and Yamanaka successfully generated mouse induced pluripotent stem(iPs)cells from somatic ceils in 2006，many laboratories around the world began relevant research on iPS and had made great progress．Reprogramming of somatic cell is a complicated process，but the specificity and mechanisms remain to be determined．Extensive experiments have been performed on hoW to improve efficiency and quality of formed iPS cells，and recently several groups independently found that inhibition of p53 cells can greatly enhance the efficiency of iPS cell formation induced from human somatic cells or mouse embryomc fibroblasts(MED． Telomere reprogramming and maintenance are important for iPS self-renewal and genomic stability．A-type lamin has been shown tO play all important role in maintaining length and function oftelomere；moreover，it could stabilize p53 protein which is all important component of DNA damage response(DDR)pathway．A-type lamin also is involved in cell differentiation during embryo development,and types of lamins di伍er during various developmental stages．Low expression levels of A-type lamins Rre characteristics of the relatively lower degree of the nucleus organization,in association with higher potential of proliferation and diffe