Author:
Poisa-Beiro Laura,Thoma Judith,Landry Jonathan,Sauer Sven,Yamamoto Akihisa,Eckstein Volker,Romanov Natalie,Raffel Simon,Hoffmann Georg F.,Bork Peer,Benes Vladimir,Gavin Anne-Claude,Tanaka Motomu,Ho Anthony D.
Abstract
AbstractInspired 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.
Funder
Deutsche Forschungsgemeinschaft
Japan Society for the Promotion of Science
Seventh Framework Programme
Publisher
Springer Science and Business Media LLC
Cited by
10 articles.
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