Adding self-renewal in committed erythroid progenitors improves the biological relevance of a mathematical model of erythropoiesis

J Theor Biol. 2008 Jan 21;250(2):322-38. doi: 10.1016/j.jtbi.2007.09.041. Epub 2007 Oct 6.

Abstract

We propose a new mathematical model of erythropoiesis that takes a positive feedback of erythrocytes on progenitor apoptosis into account, and incorporates a negative feedback of erythrocytes on progenitor self-renewal. The resulting model is a system of age-structured equations that reduces to a system of delay differential equations where the delays account for progenitor compartment duration and cell cycle length. We compare this model with experimental data on an induced-anemia in mice that exhibit damped oscillations of the hematocrit before it returns to equilibrium. When we assume no self-renewal of progenitors, we obtain an inaccurate fitting of the model with experimental data. Adding self-renewal in the progenitor compartment gives better approximations, with the main features of experimental data correctly fitted. Our results indicate the importance of progenitor self-renewal in the modelling of erythropoiesis. Moreover, the model makes testable predictions on the lifespan of erythrocytes confronted to a severe anemia, and on the progenitors behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / blood
  • Animals
  • Apoptosis / physiology
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cellular Senescence / physiology
  • Erythroid Precursor Cells / cytology*
  • Erythropoiesis / physiology*
  • Feedback, Physiological / physiology
  • Female
  • Hematocrit
  • Male
  • Mice
  • Models, Biological*