| 题名 | MicroRNA-204在胚胎干细胞分化中的功能初步研究及PEPC家族进化中的跨界HGT |
| 作者 | 彭应梅 |
| 学位类别 | 博士 |
| 答辩日期 | 2012-11 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 北京 |
| 导师 | 宿兵 |
| 关键词 | ESC miRNA-204 TGFBR2 NR4A2 PEPC |
| 其他题名 | The Function of microRNA-204 in Embryonic Stem Cells and Multiple inter-kingdom horizontal gene transfer in the evolution of phosphoenolpyruvate carboxylase gene family |
| 学位专业 | 遗传学 |
| 中文摘要 | MicroRNA是一类广泛存在于动植物基因组中的非编码小RNA。其主要通过与靶基因mRNA 3’UTR区的互补结合起到降解mRNA或者抑制翻译的作用，从而在转录后水平发挥重要的调控作用。miRNA影响着生命过程的许多方面，如胚胎发育、细胞分化、肿瘤的产生和发展等。研究表明miRNA在胚胎干细胞的自我更新和分化过程中起着重要的作用，但miRNA在ESCs向神经细胞分化过程中的作用还鲜有报道。 我们通过芯片和定量PCR技术首次发现了miRNA-204在恒河猴胚胎干细胞向神经细胞分化中可能起重要的调控作用。通过体外验证，我们发现miRNA-204可能是通过调控下游靶基因TGFBR2和NR4A2的表达实现这一作用。我们还建立了过表达miRNA-204的慢病毒载体，并成功感染了人的胚胎干细胞，感染率可达30%以上，这为我们进一步研究miRNA-204在人胚胎干细胞分化中的功能提供了条件。 此外，本论文还利用生物信息分析在磷酸烯醇丙酮酸羧化酶的演化过程中发现了大量的跨界水平基因转移现象。对该基因家族深入全面的系统发生分析有力地佐证了这些跨界水平基因转移事件的真实性，同时纠正了之前真细菌磷酸烯醇丙酮酸羧化酶来自于植物的错误观点。这一发现揭示了水平基因转移在演化中扮演的重要角色，更提示生物演化的关系可能呈现相互交错的复杂网络形态，而不是简单的树状分支形态，增进了人们对生命演化过程复杂性的认识。 |
| 英文摘要 | MicroRNA is a small molecular non-coding RNA existed in many plant and animal genomes. It functions mainly by inhibiting the translation or degradation of mRNAs through binding to its target site in the 3'UTR region of the target gene mRNAs, thus plays an important role in post-transcriptional regulation. miRNA is proved to play an important role in self-renew and differentiation of embryonic stem cells. However, whether it also plays a role during the differentiation of embryonic stem cells towards neuronal cell has not been investigated. In this thesis, by applying the microarray and quantitative real-time PCR techniques, we demonstrated for the first time that a microRNA (miRNA-204) plays an important role in differentiation of macaque's embryonic stem cells towards neuronal cells. We further discovered by in vitro assay that miRNA-204 probably functions via regulating the target gene TGFBR2 and NR4A2. In addition, we constructed lentivirous vector to over-express miRNA-204 and successfully infected human embryonic stem cells with infection rate over 30%. This provides an important resource to further investigate the function of miRNA-204 in differentiation of human embryonic stem cell. In addition, we also discovered lots of inter-kingdom horizontal gene transfers in the evolution of phosphate enolpyruvate carboxylase gene family. Further analysis of the phylogeny of this gene family supported our discovery and also corrected the previous view that bacterial type PEPC originated from plant PEPC. This finding indicates that horizontal gene transfer plays an important role in evolution, and a network rather than a tree may better represent the relationship of species in evolution. |
| 语种 | 中文 |
| 公开日期 | 2012-12-13 |
| 内容类型 | 学位论文 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7136]  |
| 专题 | 昆明动物研究所_比较基因组学 |
| 推荐引用方式 GB/T 7714 | 彭应梅. MicroRNA-204在胚胎干细胞分化中的功能初步研究及PEPC家族进化中的跨界HGT[D]. 北京. 中国科学院大学. 2012. |
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