Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells
Open accessAbstract
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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Ageing and rejuvenation of tissue stem cells and their niches
Brunet, A., Goodell, M. A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00510-w · Cited by 407 · see citing works
- 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.
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-07-14
- Volume
- 10
- Issue
- 1
- Pages
- 11597-11597
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7360735
- 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
- gold
- doi.org
- 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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