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


Journal

American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369

Informations de publication

Date de publication:
06 Nov 2023
Historique:
revised: 03 10 2023
received: 17 08 2023
accepted: 13 10 2023
medline: 6 11 2023
pubmed: 6 11 2023
entrez: 6 11 2023
Statut: aheadofprint

Résumé

Human 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.

Identifiants

pubmed: 37929634
doi: 10.1002/ajh.27145
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIDDK NIH HHS
ID : P01 DK032094
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144436
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL144436
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK32094
Pays : United States

Informations de copyright

© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.

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Auteurs

Julien Papoin (J)

Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, New York, USA.
HEMATIM, Universite de Picardie Jules Verne, Amiens, France.

Hongxia Yan (H)

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

Marjorie Leduc (M)

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

Morgane Le Gall (M)

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

Anupama Narla (A)

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

James Palis (J)

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

Laurie A Steiner (LA)

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

Patrick G Gallagher (PG)

Department of Pediatrics, Yale University, New Haven, Connecticut, USA.
Nationwide Children's Hospital, Ohio State University, Columbus, Ohio, USA.

Christopher D Hillyer (CD)

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

Emilie-Fleur Gautier (EF)

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

Narla Mohandas (N)

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

Lionel Blanc (L)

Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Division of Pediatrics Hematology/Oncology, Cohen Children's Medical Center, New Hyde Park, New York, USA.
Department of Molecular Medicine and Pediatrics, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.

Classifications MeSH