胚胎干细胞RNAs与microRNAs相互作用网络研究

发布时间：2018-12-11 21:40

【摘要】：胚胎干细胞(embryonic stem cells,简称ES细胞)是一种高度未分化细胞,具备发育成各种组织和器官的潜力,具有多能性(分化)和自我更新能力(增殖)。最近的实验[Nature463,(2010)621]研究表明：在敲掉DGCR8基因后的胚胎干细胞中,microRNAs能调节干细胞的自我更新或者促进分化。本文以胚胎干细胞中ESCCmiRNA、Lin28、c-Myc、Myc Targets、Oct4、 Pluripotency target、Let-7、DGCR8之间相互作用为研究对象,研究了胚胎干细胞中这八种生物分子之间相互作用的网络结构与胚胎干细胞功能之间的内在关系。主要研究工作和成果如下：首先,重构了干细胞中ESCCmiRNA、Lin28、c-Myc、Myc targets、Oct4、 Pluripotency target、Let-7、DGCR8之间相互作用布尔网络结构,研究了该网络结构的动力学行为,发现该相互作用网络结构具有两个稳定的状态,分别对应着胚胎干细胞的分化和增殖功能。并与随机网络结构进行了比较,发现随机网络大部分不稳定,而小部分稳定的随机网络可能对研究网络的演化有预示作用。其次,利用已有的实验数据和可能的生物学演化路径,采用基于过程的网络分解(process-based network decomposition)方法,给出了能保持生物学功能的最小网络结构,发现剩余网络对胚胎干细胞保持功能上的稳定性具有十分重要的作用。最后,对相互作用网络结构中DGCR8基因敲除进行了的研究,发现敲掉DGCR8后,得到的理论结果与文献Nature463,(2010)621中的实验结果完全一致。
[Abstract]:Embryonic stem cell (embryonic stem cells,) is a highly undifferentiated cell with the potential to develop into various tissues and organs, pluripotency (differentiation) and self-renewal (proliferation). Recent studies [Nature463, (2010) 621] have shown that in embryonic stem cells after knockout of DGCR8 gene, microRNAs can regulate self-renewal or promote differentiation of stem cells. The interaction between ESCCmiRNA,Lin28,c-Myc,Myc Targets,Oct4, Pluripotency target,Let-7,DGCR8 in embryonic stem cells was studied in this paper. The relationship between the network structure of these eight biomolecules and the function of embryonic stem cells was studied. The main work and results are as follows: firstly, the Boolean network structure of interaction between ESCCmiRNA,Lin28,c-Myc,Myc targets,Oct4, Pluripotency target,Let-7,DGCR8 in stem cells is reconstructed, and the dynamic behavior of the network is studied. It is found that the interaction network has two stable states, corresponding to the differentiation and proliferation of embryonic stem cells. Compared with the random network structure, it is found that most of the stochastic networks are unstable, while a small number of stable stochastic networks may predict the evolution of the networks. Secondly, using the existing experimental data and the possible biological evolution path, the minimal network structure which can maintain biological function is given by using the process based network decomposition (process-based network decomposition) method. It is found that the residual network plays an important role in maintaining the functional stability of embryonic stem cells. Finally, the DGCR8 gene knockout in the interacting network structure is studied. It is found that the theoretical results obtained after the knockout of DGCR8 are in good agreement with the experimental results in Nature463, (2010) 621.
【学位授予单位】：华中师范大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R329

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