Metabolomics-based elucidation of active metabolic pathways in erythrocytes and HSC-derived reticulocytes

Srivastava, Anubhav, Evans, Krystal J., Sexton, Anna E., Schofield, Louis, and Creek, Darren J. (2017) Metabolomics-based elucidation of active metabolic pathways in erythrocytes and HSC-derived reticulocytes. Journal of Proteome Research, 16 (4). pp. 1492-1505.

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Abstract

A detailed analysis of the metabolic state of human-stem-cell-derived erythrocytes allowed us to characterize the existence of active metabolic pathways in younger reticulocytes and compare them to mature erythrocytes. Using high resolution LC-MS-based untargeted metabolomics, we found that reticulocytes had a comparatively much richer repertoire of metabolites, which spanned a range of metabolite classes. An untargeted metabolomics analysis using stable-isotope-labeled glucose showed that only glycolysis and the pentose phosphate pathway actively contributed to the biosynthesis of metabolites in erythrocytes, and these pathways were upregulated in reticulocytes. Most metabolite species found to be enriched in reticulocytes were residual pools of metabolites produced by earlier erythropoietic processes, and their systematic depletion in mature erythrocytes aligns with the simplification process, which is also seen at the cellular and the structural level. Our work shows that high-resolution LC-MS-based untargeted metabolomics provides a global coverage of the biochemical species that are present in erythrocytes. However, the incorporation of stable isotope labeling provides a more accurate description of the active metabolic processes that occur in each developmental stage. To our knowledge, this is the first detailed characterization of the active metabolic pathways of the erythroid lineage, and it provides a rich database for understanding the physiology of the maturation of reticulocytes into mature erythrocytes.

Item ID: 50628
Item Type: Article (Research - C1)
ISSN: 1535-3893
Keywords: metabolomics, stable-isotope labeling, erythrocytes, reticulocytes, metabolism
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC fellowship #1088855
Date Deposited: 20 Sep 2017 10:37
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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