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07 14, 2020;10 (1): 11597.

Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells.

Laura Poisa-Beiro, Judith Thoma, Jonathan Landry, Sven Sauer, Akihisa Yamamoto, Volker Eckstein, Natalie Romanov, Simon Raffel, Georg F Hoffmann, Peer Bork, Vladimir Benes, Anne-Claude Gavin, Motomu Tanaka, Anthony D Ho
Author Information
  1. Laura Poisa-Beiro: Department of Medicine V, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
  2. Judith Thoma: Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, Im Neuenheimer Feld 253, 69120, Heidelberg, Germany.
  3. Jonathan Landry: Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117, Heidelberg, Germany.
  4. Sven Sauer: Division of Child Neurology and Metabolic Diseases, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
  5. Akihisa Yamamoto: Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, 606-8501, Japan.
  6. Volker Eckstein: Department of Medicine V, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
  7. Natalie Romanov: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117, Heidelberg, Germany.
  8. Simon Raffel: Department of Medicine V, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
  9. Georg F Hoffmann: Division of Child Neurology and Metabolic Diseases, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
  10. Peer Bork: Molecular Medicine Partnership Unit Heidelberg, EMBL and Heidelberg University, 69120, Heidelberg, Germany.
  11. Vladimir Benes: Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117, Heidelberg, Germany.
  12. Anne-Claude Gavin: Molecular Medicine Partnership Unit Heidelberg, EMBL and Heidelberg University, 69120, Heidelberg, Germany.
  13. Motomu Tanaka: Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, Im Neuenheimer Feld 253, 69120, Heidelberg, Germany. tanaka@uni-heidelberg.de.
  14. Anthony D Ho: Department of Medicine V, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. anthony_dick.ho@urz.uni-heidelberg.de.
PMID: 32665666 DOI: 10.1038/s41598-020-68396-2

Abstract

Inspired by recent proteomic data demonstrating the upregulation of carbon and glycogen metabolism in aging human hematopoietic stem and progenitor cells (HPCs, CD34+ cells), this report addresses whether this is caused by elevated glycolysis of the HPCs on a per cell basis, or by a subpopulation that has become more glycolytic. The average glycogen content in individual CD34+ cells from older subjects (> 50 years) was 3.5 times higher and more heterogeneous compared to younger subjects (< 35 years). Representative glycolytic enzyme activities in HPCs confirmed a significant increase in glycolysis in older subjects. The HPCs from older subjects can be fractionated into three distinct subsets with high, intermediate, and low glucose uptake (GU) capacity, while the subset with a high GU capacity could scarcely be detected in younger subjects. Thus, we conclude that upregulated glycolysis in aging HPCs is caused by the expansion of a more glycolytic HPC subset. Since single-cell RNA analysis has also demonstrated that this subpopulation is linked to myeloid differentiation and increased proliferation, isolation and mechanistic characterization of this subpopulation can be utilized to elucidate specific targets for therapeutic interventions to restore the lineage balance of aging HPCs.

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MeSH Term

Adult
Carbon
Cellular Senescence
Female
Glycogen
Hematopoietic Stem Cells
Humans
Male
Middle Aged
Stem Cells

Chemicals

Carbon
Glycogen
Journal Article Research Support, Non-U.S. Gov't

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