Multi-scale Modelling of Erythropoiesis and Hemoglobin Production

  • A. Bouchnita
  • A. Rocca
  • E. Fanchon
  • M. J. Koury
  • J. M. Moulis
  • V. Volpert
Article
  • 172 Downloads

Abstract

The paper is devoted to multi-scale modelling of erythropoiesis and hemoglobin production. Red blood cells, which carry oxygen from the lungs to the other body tissues, are produced in the bone marrow of adult humans in cell units called erythroblastic islands. Erythroblastic islands are composed by a central macrophage surrounded by erythroid cells in different stages of maturation. Immature cells, the colony-forming units-erythroid, make a choice between self-renewal, differentiation and apoptosis determined by the intracellular proteins and extracellular substances. Moreover, this choice is regulated by erythropoietin and other hormones. Erythropoietin is produced in the kidney in response to hypoxia from decreased numbers of red blood cells, and it is delivered in the plasma to the bone marrow. Erythropoietin stimulates differentiation of erythroid cells and increases their proliferation by downregulating apoptosis. The rate of erythropoietin production depends on the level of hemoglobin in blood which is function of the number of circulating red blood cells. Hemoglobin is produced in the erythroid cells within the bone marrow in the process of their terminal differentiation. Thus, there is a feedback between production of red blood cells by the bone marrow, the level of hemoglobin contained in these cells and the level of erythropoietin. The multi-scale model developed in this work includes erythroid cells in the bone marrow, their intracellular and extracellular regulations, hemoglobin production, and the feedback by erythropoietin. This model describes normal functioning of erythropoiesis and its response to anemia resulting from the loss of red blood cells.

Keywords

Erythropoiesis Hemoglobin Multi-scale model 

List of Abbreviations

AHSP

α-Hemoglobin stabilizing protein

ALA-S2

Mitochondrial enzyme amino-levulinate synthetase 2

BMP4

Bone morphogenetic protein 4

CFU-E/Pro-EB

Colony-forming units-erythroid/Proerythroblasts

EBI

Erythroblastic island

EPO

Erythropoietin

HIF

Hypoxia-inducible factor

HO-1

Heme oxygenase-1

HRI

Heme regulated inhibitor

HSC

Hematopoietic stem cell

IRP

Iron regulatory proteins

KL/SCF

Kit ligand/stem cell factor

TfR

Transferrin receptor

RBC

Red blood cell

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • A. Bouchnita
    • 1
    • 2
  • A. Rocca
    • 3
  • E. Fanchon
    • 3
  • M. J. Koury
    • 4
  • J. M. Moulis
    • 5
    • 6
    • 7
  • V. Volpert
    • 1
    • 8
    • 9
  1. 1.Institut Camille Jordan, UMR 5208 CNRSUniversity Lyon 1VilleurbanneFrance
  2. 2.LERMA, Mohammadia School of EngineersUniversity Mohamed VRabatMorocco
  3. 3.Université Grenoble AlpesCNRS UMR 5525, TIMC-IMAG laboratoryGrenobleFrance
  4. 4.Vanderbilt University Medical CenterNashvilleUSA
  5. 5.Université Grenoble Alpes, Laboratoire de Bioénergétique Fondamentale et Appliquée and Biologie Environmentale et Systémique (BEeSy)GrenobleFrance
  6. 6.InsermGrenobleFrance
  7. 7.Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA) Institut de Biosciences and Biotechnologies de Grenoble (BIG)GrenobleFrance
  8. 8.INRIA Team Dracula, INRIA Antenne Lyon la DouaVilleurbanneFrance
  9. 9.Laboratoire PonceletUMI 2615 CNRSMoscowRussia

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