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Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
33050 44954 2016 8 PDF Available
Title
Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells
Abstract

•We examine cell metabolism during ex vivo erythroid differentiation from HSPCs.•We demonstrate that both glycolytic and OXPHOS metabolisms are involved during proliferation.•Cells show greater reliance on OXPHOS in the differentiation phase.•We show the importance of the serum for RBC differentiation and maturation.

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.

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Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells
Publisher
Database: Elsevier - ScienceDirect
Journal: New Biotechnology - Volume 33, Issue 1, 25 January 2016, Pages 179–186
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering