论文标题

反馈信号在B淋巴管中的动态特性:一种数学建模方法

Dynamical properties of feedback signalling in B lymphopoiesis: A mathematical modelling approach

论文作者

Chulián, Salvador, Martínez-Rubio, Alvaro, Marciniak-Czochra, Anna, Stiehl, Thomas, Goñi, Cristina Blázquez, Gutiérrez, Juan Francisco Rodríguez, Orellana, Manuel Ramirez, Robleda, Ana Castillo, Pérez-García, Víctor M., Rosa, María

论文摘要

造血是血细胞产生的过程。淋巴管会产生淋巴细胞,即负责自适应免疫反应的细胞。该过程的中断与白血病等疾病有关,这在儿童中尤其出现。该过程的自我调节的特征使它们适合数学研究。 在本文中,我们使用当前可用的数据开发了淋巴细胞的数学模型。我们通过从现有的细胞谱系开发模型中汲取灵感并将其与儿科骨髓数据相结合,以特别关注调节机制。对模型进行了正式分析,从而提供稳定状态及其稳定条件。我们使用此分析来获得参数空间的生物学相关区域,并了解B细胞翻新的动力学行为。最后,我们使用数值模拟来进一步了解增殖和成熟速率对B线中细胞重建的影响。我们得出的结论是,包括细胞增殖的反馈调节的模型代表了骨髓中B细胞重建的生物学上合理的描述。血液学疾病的研究可能会受益于B淋巴管的精确动力学描述。

Haematopoiesis is the process of generation of blood cells. Lymphopoiesis generates lymphocytes, the cells in charge of the adaptive immune response. Disruptions of this process are associated with diseases like leukaemia, which is especially incident in children. The characteristics of self-regulation of this process make them suitable for a mathematical study. In this paper we develop mathematical models of lymphopoiesis using currently available data. We do this by drawing inspiration from existing structured models of cell lineage development and integrating them with paediatric bone marrow data, with special focus on regulatory mechanisms. A formal analysis of the models is carried out, giving steady states and their stability conditions. We use this analysis to obtain biologically relevant regions of the parameter space and to understand the dynamical behaviour of B-cell renovation. Finally, we use numerical simulations to obtain further insight into the influence of proliferation and maturation rates on the reconstitution of the cells in the B line. We conclude that a model including feedback regulation of cell proliferation represents a biologically plausible depiction for B-cell reconstitution in bone marrow. Research into haematological disorders could benefit from a precise dynamical description of B lymphopoiesis.

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