Phenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways

Author:

Papoin Julien12ORCID,Yan Hongxia3,Leduc Marjorie4,Le Gall Morgane4,Narla Anupama5,Palis James6,Steiner Laurie A.6,Gallagher Patrick G.78,Hillyer Christopher D.3,Gautier Emilie‐Fleur4ORCID,Mohandas Narla3ORCID,Blanc Lionel1910ORCID

Affiliation:

1. Institute of Molecular Medicine Feinstein Institutes for Medical Research Manhasset New York USA

2. HEMATIM Universite de Picardie Jules Verne Amiens France

3. Red Cell Physiology Laboratory Lindsey F. Kimball Research Institute, New York Blood Center New York New York USA

4. Proteom'IC facility Université Paris Cité, CNRS, INSERM, Institut Cochin Paris France

5. Division of Hematology‐Oncology, Department of Pediatrics Stanford University School of Medicine Palo Alto California USA

6. Center for Child Health Research University of Rochester Rochester New York USA

7. Department of Pediatrics Yale University New Haven Connecticut USA

8. Nationwide Children's Hospital Ohio State University Columbus Ohio USA

9. Division of Pediatrics Hematology/Oncology Cohen Children's Medical Center New Hyde Park New York USA

10. Department of Molecular Medicine and Pediatrics Zucker School of Medicine at Hofstra/Northwell Hempstead New York USA

Abstract

AbstractHuman erythropoiesis is a complex process leading to the production of 2.5 million red blood cells per second. Following commitment of hematopoietic stem cells to the erythroid lineage, this process can be divided into three distinct stages: erythroid progenitor differentiation, terminal erythropoiesis, and reticulocyte maturation. We recently resolved the heterogeneity of erythroid progenitors into four different subpopulations termed EP1–EP4. Here, we characterized the growth factor(s) responsiveness of these four progenitor populations in terms of proliferation and differentiation. Using mass spectrometry‐based proteomics on sorted erythroid progenitors, we quantified the absolute expression of ~5500 proteins from EP1 to EP4. Further functional analyses highlighted dynamic changes in cell cycle in these populations with an acceleration of the cell cycle during erythroid progenitor differentiation. The finding that E2F4 expression was increased from EP1 to EP4 is consistent with the noted changes in cell cycle. Finally, our proteomic data suggest that the protein machinery necessary for both oxidative phosphorylation and glycolysis is present in these progenitor cells. Together, our data provide comprehensive insights into growth factor‐dependence of erythroid progenitor proliferation and the proteome of four distinct populations of human erythroid progenitors which will be a useful framework for the study of erythroid disorders.

Funder

National Heart, Lung, and Blood Institute

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Wiley

Subject

Hematology

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