Modeling of the inherence of feedback regulation and stem cell behavior in granulopoiesis
Modeling of the inherence of feedback regulation and stem cell behavior in granulopoiesis
复制标题
粒细胞生成中反馈调节和干细胞行为的固有模型
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
S. Koizumi
中科院分区：
文献类型：
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作者：
Y. Saikawa;T. Komatsuzaki;R. Nishimura;Hideaki Maeba;T. Uehara;S. Koizumi
造血干细胞(HSC)的自我维持和分化承诺机制以及外周造血调控机制一直是造血研究中的热点问题。在本研究中，我们将三维细胞自动机(CA)模型应用于粒细胞生成，以确定造血过程的微观机制和宏观行为之间的内在生成理论关系。模型参数包括增殖期细胞的有丝分裂事件数、从HSC到成熟细胞的15个不同阶段(T1~T15和HSC复制时间的Tdup)以及HSC自我更新的邻域规则。当满足以下转运时间的不等式时，动态平衡的粒细胞生成被实现：T1>；Σtn和tdup>；1/2t1。重要的是，外周粒细胞数量的外部扰动以负反馈的方式诱导了细胞生产的稳定。单个HSC的Tdup剧烈波动，以产生对这种扰动做出反应的后代。单细胞动力学分析表明，HSC的对称性或非对称性细胞分裂是以过渡方式招募的，从而产生了对谱系承诺过程的调节作用。反馈调节的内在规律性将是造血系统涌现动力学特性的特征。CA模型将为分析HSC的行为和了解血液系统疾病的异常动力学提供框架。
Long-standing controversies in hematopoiesis include the mechanisms of self-maintenance and differentiation commitment of the hematopoietic stem cells (HSC), and regulation of the peripheral control of hematopoiesis. In the present study, we have applied a three-dimensional cellular automaton (CA) model to granulopoiesis in order to identify the internally generative theoretical relationship between microscopic mechanisms and macroscopic behavior of hematopoietic processes. The number of mitotic events of the cells in a proliferating phase, the transit time of each of 15 differential stages from HSC to mature cells (T1 to T15, and Tdup for HSC duplication time), and the neighborhood rules for HSC self-renewal were incorporated in this model system as analytical parameters. Homeostatic granulopoiesis was achieved when the following inequalities for the transit times were fulfilled: T 1 > Σ Tn and Tdup > 1/2 T1. Importantly, stabilization of the cell production was induced in a negative feedback manner following external perturbation of the peripheral granulocyte numbers. The Tdup of individual HSC dramatically fluctuated to produce the offspring responding to this perturbation. A single cell kinetic analysis demonstrated that symmetrical or asymmetrical cell division of the HSC was recruited in a transitional manner resulting in generation of the regulatory effect on the lineage-commitment processes. The inherence of feedback regulation would be a characteristic feature of the emergent dynamical property in the hematopoietic system. The CA modeling will provide the framework to analyze the behavior of HSC and to understand 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