Université de Lyon, Université Lyon 1, CNRS, UMR 5208, Institut Camille Jordan, Batiment du Doyen Jean Braconnier, 43, blvd du 11 novembre 1918, F - 69222 Villeurbanne Cedex, France.
J Theor Biol. 2010 Apr 7;263(3):303-16. doi: 10.1016/j.jtbi.2009.12.026. Epub 2010 Jan 4.
This work is devoted to mathematical modelling of erythropoiesis. We propose a new multi-scale model, in which we bring together erythroid progenitor dynamics and intracellular regulatory network that determines erythroid cell fate. All erythroid progenitors are divided into several sub-populations according to their maturity. Two intracellular proteins, Erk and Fas, are supposed to be determinant for regulation of self-renewal, differentiation and apoptosis. We consider two growth factors, erythropoietin and glucocorticoids, and describe their dynamics. Several feedback controls are introduced in the model. We carry out computer simulations of anaemia and compare the obtained results with available experimental data on induced anaemia in mice. The main objective of this work is to evaluate the roles of the feedback controls in order to provide more insights into the regulation of erythropoiesis. Feedback by Epo on apoptosis is shown to be determinant in the early stages of the response to anaemia, whereas regulation through intracellular regulatory network, based on Erk and Fas, appears to operate on a long-term scale.
这项工作致力于红细胞生成的数学建模。我们提出了一个新的多尺度模型，其中我们将红细胞祖细胞动力学和决定红细胞命运的细胞内调控网络结合在一起。根据成熟度，所有的红细胞祖细胞被分为几个亚群。两种细胞内蛋白，Erk 和 Fas，被认为是自我更新、分化和凋亡调控的决定因素。我们考虑了两种生长因子，促红细胞生成素和糖皮质激素，并描述了它们的动力学。模型中引入了几种反馈控制。我们对贫血进行了计算机模拟，并将得到的结果与在小鼠中诱导贫血的现有实验数据进行了比较。这项工作的主要目的是评估反馈控制的作用，以便更深入地了解红细胞生成的调控。促红细胞生成素对细胞凋亡的反馈在对贫血的早期反应中起决定作用，而基于 Erk 和 Fas 的细胞内调控网络的调节则在长期尺度上起作用。
