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揭示细胞命运决定过程中的分子调控机制对理解干细胞分化和组织稳态的建立和维持具有决定性的意义.本文通过归纳从机制研究中积累的分子调控关系,构建了血液系统髓系细胞分化相关的粗粒化内源性网络.通过对网络动力学进行定量分析,本文以稳态的概念对髓系主要细胞类型进行分类,并定量预测了一系列细胞类型转换过程中出现的中间状态或过渡态.基于计算结果和数学中动力学系统的原理,本文提出了髓系细胞发育景观拓扑图,并从高维非线性动力系统的基本特性出发,讨论了实验中在特定基因操作下观测到的转分化现象,并预测了相应过程中的分子动力学变化.本研究表明,髓系细胞发育定量景观拓扑图的构建有助于全局性地阐述恶性肿瘤和再生障碍性疾病的发生发展.
It is of decisive significance to reveal the molecular regulation mechanism during the process of cell fate decision to understand the establishment and maintenance of stem cell differentiation and tissue homeostasis.In this paper, we conclude that the molecular relationship of myeloid cell differentiation Coarse-grained endogenous network.Through the quantitative analysis of network dynamics, this paper classifies the main cell types of myeloid by the concept of steady-state and quantitatively predicts a series of intermediate states or transitional states Based on the computational results and the principles of the dynamical system in mathematics, this paper presents a topological map of the myeloid cell development landscape. Based on the basic characteristics of the high dimensional nonlinear dynamical system, the transdifferentiation phenomenon observed under specific gene manipulations , And predict the molecular dynamics changes in the corresponding process.The present study shows that the quantitative topological map of myeloid cell development helps to explain the occurrence and development of malignant tumors and aplastic diseases in a global way.