title: Adding self-renewal in committed erythroid progenitors improves the biological relevance of a mathematical model of erythropoiesis.
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.
authors.affiliation: Université de Lyon, Université Lyon 1, CNRS, UMR 5208, Institut Camille Jordan, Btiment du Doyen Jean Braconnier, 43, blvd du 11 novembre 1918, F - 69222 Villeurbanne Cedex, France. crauste@math.univ-lyon1.fr
authors.forename: Fabien
authors.initials: F
authors.lastname: Crauste
authors.forename: Laurent
authors.initials: L
authors.lastname: Pujo-Menjouet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Génieys
authors.forename: Clément
authors.initials: C
authors.lastname: Molina
authors.forename: Olivier
authors.initials: O
authors.lastname: Gandrillon
mesh_terms: D000740:Anemia / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000166:cytology*; D004920:Erythropoiesis / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D006400:Hematocrit; D008297:Male; D051379:Mice; D008954:Models, Biological