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Glucose metabolism and aging of hematopoietic stem and progenitor cells

Published inInternational journal of molecular sciences, vol. 23, no. 6, 3028
Publication date2022-03-11
First online date2022-03-11
Abstract

Comprehensive proteomics studies of human hematopoietic stem and progenitor cells (HSPC) have revealed that aging of the HSPC compartment is characterized by elevated glycolysis. This is in addition to deregulations found in murine transcriptomics studies, such as an increased differentiation bias towards the myeloid lineage, alterations in DNA repair, and a decrease in lymphoid development. The increase in glycolytic enzyme activity is caused by the expansion of a more glycolytic HSPC subset. We therefore developed a method to isolate HSPC into three distinct categories according to their glucose uptake (GU) levels, namely the GUhigh, GUinterand GUlowsubsets. Single-cell transcriptomics studies showed that the GUhighsubset is highly enriched for HSPC with a differentiation bias towards myeloid lineages. Gene set enrichment analysis (GSEA) demonstrated that the gene sets for cell cycle arrest, senescence-associated secretory phenotype, and the anti-apoptosis and P53 pathways are significantly upregulated in the GUhighpopulation. With this series of studies, we have produced a comprehensive proteomics and single-cell transcriptomics atlas of molecular changes in human HSPC upon aging. Although many of the molecular deregulations are similar to those found in mice, there are significant differences. The most unique finding is the association of elevated central carbon metabolism with senescence. Due to the lack of specific markers, the isolation and collection of senescent cells have yet to be developed, especially for human HSPC. The GUhighsubset from the human HSPC compartment possesses all the transcriptome characteristics of senescence. This property may be exploited to accurately enrich, visualize, and trace senescence development in human bone marrow.

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Keywords
  • Aging
  • Central carbon metabolism
  • Glycolysis
  • Hematopoietic stem and progenitor cells
  • Senescence signature
  • Aging / genetics
  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Glucose / metabolism
  • Hematopoietic Stem Cells / metabolism
  • Mice
Citation (ISO format)
POISA-BEIRO, Laura et al. Glucose metabolism and aging of hematopoietic stem and progenitor cells. In: International journal of molecular sciences, 2022, vol. 23, n° 6, p. 3028. doi: 10.3390/ijms23063028
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ISSN of the journal1422-0067
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Creation05/04/2022 2:07:00 PM
First validation05/04/2022 2:07:00 PM
Update time03/16/2023 6:28:59 AM
Status update03/16/2023 6:28:58 AM
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