Emergent Properties of Feedback Regulation and Stem Cell Behavior in a Granulopoiesis Model as a Complex System
Emergent Properties of Feedback Regulation and Stem Cell Behavior in a Granulopoiesis Model as a Complex System
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作为复杂系统的粒细胞生成模型中反馈调节和干细胞行为的涌现特性
作者：
Y. Saikawa;T. Komatsuzaki
为了确定造血过程作为一个复杂系统的微观机制和宏观行为之间的内在生成理论关系，通过开发细胞自动机（CA）模型，利用计算机模拟粒细胞生成。造血干细胞（HSCs）在三维空间中分布增殖和分化。增殖期细胞的有丝分裂事件的数量、从HSC进展到成熟细胞的15个不同阶段中的每一个的转运时间（T）、HSC的复制时间（Tdup）和细胞增殖的邻域规则都被并入作为该空间中的分析参数。成功实现了源自单个HSC的稳态粒细胞生成。一个重要的部分是稳定的细胞生产诱导的负反馈的方式后，外部扰动的外周粒细胞数量。单细胞动力学分析将分化细胞和HSC的行为描述为响应于反馈动力学而波动其T和自我更新时间（Tdup）。HSC的随机细胞分裂以过渡的方式被招募，从而产生对分化-定型过程的调节作用。在粒细胞生成系统中，局部细胞相互作用产生全局动力学的概念被CA模型具体化。这种方法将提供一个框架，分析造血干细胞的行为，并使造血疾病的异常动力学的理解。
To identify the internally generative theoretical relationship between microscopic mechanisms and the macroscopic behavior of hematopoietic processes as a complex system, a computer simulation of granulopoiesis was exploited by developing a cellular automaton (CA) model. Hematopoietic stem cells (HSCs) distribute themselves to proliferate and differentiate in a three-dimensional analytical space. The number of mitotic events of the cells in a proliferating phase, the transit times (T) of each of 15 differential stages progressing from a HSC to a mature cell, the duplication times (Tdup) of HSCs, and the neighborhood rules for cell proliferation were all incorporated as analytical parameters in this space. Homeostatic granulopoiesis originating from a single HSC was successfully achieved. An important part is the stabilization of cell production induced by way of negative feedback following external perturbation of the peripheral granulocyte numbers. Single-cell kinetic analyses describe the behavior of differentiating cells and HSCs as fluctuating their T and self-renewal time (Tdup) in response to the feedback dynamics. Stochastic cell divisions of HSCs were recruited in a transitional manner resulting in the generation of a regulatory effect on the differentiation–commitment processes. The concept that local cellular interaction produces global dynamics in a granulopoietic system was reified by CA modeling. This approach will provide a framework for analyzing the behavior of HSCs and enable an understanding of the abnormal kinetics of hematopoietic diseases.
粒细胞生成和慢性粒细胞白血病的数学模型。
影响因子：
11.2
作者：
Fokas,AS;Keller,JB;Clarkson,BD
通讯作者：
Clarkson,BD
造血干细胞基因治疗策略：计算机模拟研究的见解。
影响因子：
20.3
作者：
Abkowitz,JL;Catlin,SN;Guttorp,P
通讯作者：
Guttorp,P