ArticleHaematologica2022
Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Bone as a Biomarker of Ageing and Senescence: Connecting Musculoskeletal Health to Longevity via Diet, Nutrition and Exercise.Biology · 2026Review
- Aging mechanisms and rejuvenation strategies for hematopoietic stem cells.Genome biology · 2026Review
- Molecular and phenotypic blueprint of human hematopoiesis links proliferation stress to stem cell aging.The Journal of experimental medicine · 2026Article
- Hematopoietic (stem) cells-The elixir of life?FEBS letters · 2026Review
- Cdc42 interacts with chaperone Ydj1 to enhance its stability and partitioning during asymmetric cell division and aging in yeast.PLoS biology · 2026Article
- An inflammatory and quiescent HSC subpopulation expands with age in humans.Genome biology · 2026Article
- Lessons in longevity from blood stem cells under protein stress.Trends in cell biology · 2026Review
- Article
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- Control of stress-activated Cdc42 dynamics by the MAP kinase Sty1-NDR kinase Orb6 regulatory axis.iScience · 2025Article
- Loss of DCAF8 impairs hematopoietic stem cell function with cellular senescence via the DOCK11-CDC42 axis.Blood · 2025Article
- An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans.bioRxiv : the preprint server for biology · 2025Article
- KLHL23 and RhoGDI coordinate CDC42 inactivation ensuring membrane homeostasis.Nature chemical biology · 2025Article
- Cell polarity: cell type-specific regulators, common pathways, and polarized vesicle transport.Leukemia · 2025Review
- Immunological biomarkers of aging.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- The role of the haematopoietic stem cell niche in development and ageing.Nature reviews. Molecular cell biology · 2025Review
- Hematopoietic stem cell size heterogeneity is not linked to changes in stem cell potential of aged HSCs.Frontiers in aging · 2025Article
- Article
- Quantitative determination of the spatial distribution of components in single cells with CellDetail.Nature communications · 2024Article
- Rejuvenating aged stem cells: therapeutic strategies to extend health and lifespan.FEBS letters · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we characterize age-related phenotypes of human hematopoietic stem cells (HSC). We report increased frequencies of HSC, hematopoietic progenitor cells and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSC further exhibited a delay in initiating division ex vivo though without changes in their division kinetics. The activity of the small RhoGTPase Cdc42 was elevated in aged human hematopoietic cells and we identified a positive correlation between Cdc42 activity and the frequency of HSC upon aging. The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarization of aged human HSC with respect to Cdc42. Elevated activity of Cdc42 in aged HSC thus contributed to age-related changes in HSC. Xenotransplant, using NBSGW mice as recipients, showed elevated chimerism in recipients of aged compared to young HSC. Aged HSC treated with CASIN ex vivo displayed an engraftment profile similar to recipients of young HSC. Taken together, our work reveals strong evidence for a role of elevated Cdc42 activity in driving aging of human HSC, and similar to mice, this presents a likely possibility for attenuation of aging in human HSC.
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