title: Mathematical modeling reveals differential effects of erythropoietin on proliferation and lineage commitment of human hematopoietic progenitors in early erythroid culture.
abstract: Erythropoietin is essential for the production of mature erythroid cells, promoting both proliferation and survival. Whether erythropoietin and other cytokines can influence lineage commitment of hematopoietic stem and progenitor cells is of significant interest. To study lineage restriction of the common myeloid progenitor to the megakaryocyte/erythroid progenitor of peripheral blood CD34(+) cells, we have shown that the cell surface protein CD36 identifies the earliest lineage restricted megakaryocyte/erythroid progenitor. Using this marker and carboxyfluorescein succinimidyl ester to track cell divisions in vitro, we have developed a mathematical model that accurately predicts population dynamics of erythroid culture. Parameters derived from the modeling of cultures without added erythropoietin indicate that the rate of lineage restriction is not affected by erythropoietin. By contrast, megakaryocyte/erythroid progenitor proliferation is sensitive to erythropoietin from the time that CD36 first appears at the cell surface. These results shed new light on the role of erythropoietin in erythropoiesis and provide a powerful tool for further study of hematopoietic progenitor lineage restriction and erythropoiesis.
authors.affiliation: Department of Engineering Mathematics, Faculty of Engineering, University of Bristol.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ward
authors.affiliation: School of Biochemistry, Faculty of Medical and Veterinary Science, University of Bristol, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Carter
authors.affiliation: Department of Engineering Mathematics, Faculty of Engineering, University of Bristol.
authors.forename: Martin
authors.initials: M
authors.lastname: Homer
authors.affiliation: Department of Engineering Mathematics, Faculty of Engineering, University of Bristol.
authors.forename: Lucia
authors.initials: L
authors.lastname: Marucci
authors.affiliation: School of Biochemistry, Faculty of Medical and Veterinary Science, University of Bristol, UK a.gampel@bristol.ac.uk.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gampel
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects*; D058948:Cell Tracking; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015233:Models, Statistical; D061251:Primary Cell Culture; D019089:Stem Cell Factor / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D018955:CD36 Antigens; C508596:IL3 protein, human; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007377:Interleukin-3; D019089:Stem Cell Factor; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I