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hal-00596682, version 1

Modelling Erythroblastic Islands: Using a Hybrid Model to Assess the Function of Central Macrophage

Stephan Fischer () 1, Polina Kurbatova () 23, Nikolai Bessonov 4, Olivier Gandrillon () 35, Vitaly Volpert (Author to contact preferably) 23, Fabien Crauste () 23

(2011-05-12)

Abstract: The production and regulation of red blood cells, erythropoiesis, occurs in the bone marrow where erythroid cells proliferate and differentiate within particular struc- tures, called erythroblastic islands. A typical structure of these islands consists in a macrophage (white cell) surrounded by immature erythroid cells (progenitors), with more mature cells on the periphery of the island, ready to leave the bone marrow and enter the bloodstream. A hybrid model, coupling a continuous model (ordinary dif- ferential equations) describing intracellular regulation through competition of two key proteins, to a discrete spatial model describing cell-cell interactions, with growth factor diffusion in the medium described by a continuous model (partial differential equations), is proposed to investigate the role of the central macrophage in normal erythropoiesis. Intracellular competition of the two proteins leads the erythroid cell to either prolifer- ation, differentiation, or death by apoptosis. This approach allows considering spatial aspects of erythropoiesis, involved for instance in the occurrence of cellular interactions or the access to external factors, as well as dynamics of intracellular and extracellular scales of this complex cellular process, accounting for stochasticity in cell cycle durations and orientation of the mitotic spindle. The analysis of the model shows a strong effect of the central macrophage on the stability of an erythroblastic island, when assuming the macrophage releases pro-survival cytokines. Even though it is not clear whether or not erythroblastic island stability must be required, investigation of the model concludes that stability improves responsiveness of the model, hence stressing out the potential relevance of the central macrophage in normal erythropoiesis.

  • 1:  COMBINING (LIRIS / INRIA Grenoble Rhône-Alpes / INSA Lyon / UCB Lyon)
  • INRIA – Université Claude Bernard - Lyon I – Laboratoire d'informatique en Image et Systèmes d'Information – CNRS : UMR5205 – Institut National des Sciences Appliquées (INSA) - Lyon
  • 2:  Institut Camille Jordan (ICJ)
  • CNRS : UMR5208 – Université Claude Bernard - Lyon I – Ecole Centrale de Lyon – Institut National des Sciences Appliquées (INSA) - Lyon
  • 3:  DRACULA (INRIA Grenoble Rhône-Alpes / Institut Camille Jordan)
  • INRIA – CNRS : UMR5534 – Université Claude Bernard - Lyon I : EA – Institut Camille Jordan
  • 4:  Institute of Problems of Mechanical Engineering [St. Petersburg] (IPME)
  • Russian Academy of Science
  • 5:  Centre de génétique moléculaire et cellulaire (CGMC)
  • CNRS : UMR5534 – Université Claude Bernard - Lyon I
  • Collaboration : INRIA project-team "Dracula"; ANR grant ANR-09-JCJC-0100-01; project ProCell; ANR Project Bimod
  • Domain : Computer Science/Modeling and Simulation
    Life Sciences/Quantitative Methods
    Computer Science/Bioinformatics
    Physics/Physics/Biological Physics
  • Keywords : Hybrid model – erythropoiesis – erythroblastic islands – macrophage – regulatory networks
  • Internal note : UMR5208
 
  • hal-00596682, version 1
  • oai:hal.archives-ouvertes.fr:hal-00596682
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  • Submitted on: Sunday, 29 May 2011 16:08:29
  • Updated on: Tuesday, 31 May 2011 12:02:09