Cited by 23Hematopoietic Stem Cell TransplantationCancer, Hypoxia, and MetabolismMesenchymal stem cell research

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

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Poisa-Beiro, Laura, Thoma, Judith, Landry, Jonathan, Sauer, Sven, Yamamoto, Akihisa, Eckstein, Volker, Romanov, Natalie, Raffel, Simon +6 more·2020·Scientific Reports

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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Authors
Poisa-Beiro, L., Thoma, J., Landry, J., Sauer, S., Yamamoto, A., Eckstein, V., Romanov, N., Raffel, S., Hoffmann, G. F., Bork, P., Benes, V., Gavin, A.-C., Tanaka, M., & Ho, A. D.
Affiliations
  • Heidelberg University (DE)
  • Kyoto University (JP)
  • European Molecular Biology Laboratory (DE)
  • University Hospital Heidelberg (DE)
  • Max Planck Institute of Biophysics (DE)
  • University of Geneva (CH)
Corresponding author
  • Tanaka, Motomu
  • Ho, Anthony D.
Venue
Scientific Reports
Published
2020-07-14
Volume
10
Issue
1
Pages
11597-11597
ISSN
2045-2322 (ISSN-L)
OpenAlex
W3043593628
Cited by
23
References
41
Citations by year
2026: 6 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 1
FWCI
1.74
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (CRC873 B7)
  • Japan Society for the Promotion of Science (20H00661)
  • Seventh Framework Programme (306240)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
hematopoietic stem and progenitor cells, aging, glycogen accumulation, glycolysis, glucose uptake, central carbon metabolism, CD34+ cells, myeloid differentiation, cell proliferation, single-cell RNA sequencing
MeSH terms
Adult, Carbon, Female, Glycogen, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Stem Cells, Cellular Senescence

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