Mathematical study of feedback control roles and relevance in stress erythropoiesis.

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.