title: Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells.
abstract: An understanding of the metabolic profile of cell proliferation and differentiation should support the optimization of culture conditions for hematopoietic stem and progenitor cell (HSPC) proliferation, differentiation, and maturation into red blood cells. We have evaluated the key metabolic parameters during each phase of HSPC culture for red blood cell production in serum-supplemented (SS) and serum-free (SF) conditions. A simultaneous decrease in growth rate, total protein content, cell size, and the percentage of cells in the S/G2 phase of cell cycle, as well as an increase in the percentage of cells with a CD71(-)/GpA(+) surface marker profile, indicates HSPC differentiation into red blood cells. Compared with proliferating HSPCs, differentiating HSPCs showed significantly lower glucose and glutamine consumption rates, lactate and ammonia production rates, and amino acid consumption and production rates in both SS and SF conditions. Furthermore, extracellular acidification was associated with late proliferation phase, suggesting a reduced cellular metabolic rate during the transition from proliferation to differentiation. Under both SS and SF conditions, cells demonstrated a high metabolic rate with a mixed metabolism of both glycolysis and oxidative phosphorylation (OXPHOS) in early and late proliferation, an increased dependence on OXPHOS activity during differentiation, and a shift to glycolytic metabolism only during maturation phase. These changes indicate that cell metabolism may have an important impact on the ability of HSPCs to proliferate and differentiate into red blood cells.
authors.affiliation: School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Hasbullah
authors.initials: H
authors.lastname: Daud
authors.affiliation: School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Browne
authors.affiliation: School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Ireland; Institute of Laser for Postgraduate Studies, University of Baghdad, Iraq.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Al-Majmaie
authors.affiliation: School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Irish Blood Transfusion Services, Dublin, Ireland.
authors.forename: William
authors.initials: W
authors.lastname: Murphy
authors.affiliation: School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: m.al-rubeai@ucd.ie.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Rubeai
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*
chemical_list: D000596:Amino Acids