粗粒内源性网络可预测血液系统髓系细胞分化和转分化的主要时序特征

发布时间：2018-01-12 19:24

本文关键词：粗粒内源性网络可预测血液系统髓系细胞分化和转分化的主要时序特征　出处：《中国科学:生命科学》2017年06期 　论文类型：期刊论文

【摘要】：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.
[Abstract]:It is very important to reveal the molecular regulation mechanism in the process of cell fate determination for understanding the establishment and maintenance of stem cell differentiation and tissue homeostasis. A coarse-grained endogenous network related to the differentiation of myeloid cells in blood system was constructed. Through quantitative analysis of network dynamics, the main cell types of myeloid were classified by the concept of steady-state. A series of intermediate states or transition states in the course of cell type conversion were quantitatively predicted. Based on the results of calculation and the principle of dynamic system in mathematics, a landscape topology map of myeloid cell development was proposed in this paper. Based on the basic characteristics of high dimensional nonlinear dynamic systems, the transdifferentiation phenomena observed in experiments under the operation of specific genes are discussed, and the molecular dynamics changes in the corresponding processes are predicted. The construction of quantitative landscape topograph of medullary cell development is helpful to explain the occurrence and development of malignant tumor and aplastic disease.
【作者单位】：上海交通大学系统生物医学研究院系统生物医学教育部重点实验室;上海交通大学生物医学工程学院;上海交通大学医学院上海肿瘤研究中心国家重点实验室;上海大学定量生命科学国际研究中心和物理系;
【基金】：国家自然科学基金(批准号:91529306,91329301,91652930016)资助
【分类号】：R331
【正文快照】： 血液是人体中一类快速进行自我更新的组织,包含诸多具有不同功能的细胞类型.由于血细胞本身流动的生活模式,及其易分离易培养等诸多优良特性,被广泛应用于研究干细胞分化和细胞命运决定过程中,并积累了大量研究成果.在过去的研究中,根据细胞表面抗原的表达,人们从实验中分离出

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