Mathematical modelling reveals differential effects of erythropoietin on proliferation and lineage commitment of human hematopoietic progenitors in early erythroid culture

Daniel T Ward, Deborah A Carter, Martin E Homer, Lucia Marucci, Alexandra Gampel

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
291 Downloads (Pure)

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 modelling 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.
Original languageEnglish
Pages (from-to)286-296
Number of pages11
JournalHaematologica
Volume101
Issue number3
Early online date23 Nov 2015
DOIs
Publication statusPublished - 29 Feb 2016

Keywords

  • lineage commitment
  • erythropoietin
  • mathematical model
  • erythroid progenitor
  • cell proliferation
  • hematopoietic progenitor

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