Duchesne Ronan, Guillemin Anissa, Crauste Fabien, Gandrillon Olivier
Laboratoire de Biologie et Modélisation de la Cellule, CNRS UMR 5239, École Normale Supérieure de Lyon, 46 allée d'Italie, Lyon.
Inria team Dracula, Inria center Grenoble-Rhône Alpes, 56 Boulevard Niels Bohr, Villeurbanne.
In Silico Biol. 2019;13(1-2):55-69. doi: 10.3233/ISB-190471.
The in vivo erythropoiesis, which is the generation of mature red blood cells in the bone marrow of whole organisms, has been described by a variety of mathematical models in the past decades. However, the in vitro erythropoiesis, which produces red blood cells in cultures, has received much less attention from the modelling community. In this paper, we propose the first mathematical model of in vitro erythropoiesis. We start by formulating different models and select the best one at fitting experimental data of in vitro erythropoietic differentiation obtained from chicken erythroid progenitor cells. It is based on a set of linear ODE, describing 3 hypothetical populations of cells at different stages of differentiation. We then compute confidence intervals for all of its parameters estimates, and conclude that our model is fully identifiable. Finally, we use this model to compute the effect of a chemical drug called Rapamycin, which affects all states of differentiation in the culture, and relate these effects to specific parameter variations. We provide the first model for the kinetics of in vitro cellular differentiation which is proven to be identifiable. It will serve as a basis for a model which will better account for the variability which is inherent to the experimental protocol used for the model calibration.
体内红细胞生成是指在整个生物体的骨髓中产生成熟红细胞的过程，在过去几十年里，已经有各种数学模型对其进行了描述。然而，体外红细胞生成，即在培养物中产生红细胞的过程，受到建模界的关注要少得多。在本文中，我们提出了第一个体外红细胞生成的数学模型。我们首先构建不同的模型，并在拟合从鸡红细胞祖细胞获得的体外红细胞生成分化实验数据时选择最佳模型。它基于一组线性常微分方程，描述了处于不同分化阶段的3个假设细胞群体。然后我们计算其所有参数估计值的置信区间，并得出我们的模型是完全可识别的结论。最后，我们使用这个模型来计算一种名为雷帕霉素的化学药物的作用，该药物会影响培养物中所有分化状态，并将这些作用与特定的参数变化联系起来。我们提供了第一个体外细胞分化动力学模型，该模型已被证明是可识别的。它将作为一个模型的基础，该模型将更好地解释用于模型校准的实验方案所固有的变异性。
