Fetal and adult hemoglobin production during adult erythropoiesis: Coordinate expression correlates with cell proliferation

Urszula Wojda, Pierre Noel, Jeffery L. Miller

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The design and evaluation of therapies for the sickle cell and β-thalassemia syndromes rely on our understanding of hemoglobin accumulation during human erythropoiesis. Here we report direct measurements of hemoglobin composition and messenger RNA (mRNA) levels in cultured CD34+ cells and correlate those measurements with studies of freshly obtained bone marrow samples. Hemoglobin levels in differentiating cells were also compared with morphologic, immunophenotypic, and cell cycle assessments. A population of large preproerythroblasts was first identified within 24 hours and became the dominant population by day 5. The transition from proerythroblast to basophilic normoblast occurred later, from days 7 to 9, and correlated with a peak of 74.1 ± 3.9% of the cells in the S phase of cell cycle. Orthochromatic normoblasts were the dominant and final cell type by day 13. High-performance liquid chromatographybased quantitation of fetal (HbF) and adult (HbA) hemoglobin and real-time polymerase chain reaction globin mRNA quantitation demonstrated a coordinate rise in the accumulation of both proteins and mRNA among these developmentally staged populations. Quantitative analyses on freshly sorted bone marrow populations demonstrated a similar rising pattern with β-globin and HbA as the dominant species at both early and late stages of differentiation. We found no evidence for HbF dominant populations or switching during differentiation in adult cells. Instead, rapid increases in both HbF (heterocellular) and HbA (pancellular) content were observed, which coincided with the apex in cell cycling and the proerythroblast-basophilic normoblast transition. Based on these measurements, we conclude that HbF and HbA content are regulated with the rate of proliferation during adult erythropoiesis.

Original languageEnglish (US)
Pages (from-to)3005-3013
Number of pages9
JournalBlood
Volume99
Issue number8
DOIs
StatePublished - Apr 15 2002
Externally publishedYes

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Fetal Hemoglobin
Erythroblasts
Erythropoiesis
Cell proliferation
Hemoglobins
Cell Proliferation
Globins
Messenger RNA
Population
Bone
Cells
Cell Cycle
Bone Marrow
Polymerase chain reaction
Thalassemia
Cell- and Tissue-Based Therapy
S Phase
Real-Time Polymerase Chain Reaction
Cultured Cells
Liquids

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Fetal and adult hemoglobin production during adult erythropoiesis : Coordinate expression correlates with cell proliferation. / Wojda, Urszula; Noel, Pierre; Miller, Jeffery L.

In: Blood, Vol. 99, No. 8, 15.04.2002, p. 3005-3013.

Research output: Contribution to journalArticle

Wojda, Urszula ; Noel, Pierre ; Miller, Jeffery L. / Fetal and adult hemoglobin production during adult erythropoiesis : Coordinate expression correlates with cell proliferation. In: Blood. 2002 ; Vol. 99, No. 8. pp. 3005-3013.
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