Dynamic Changes in Mouse Hematopoietic Stem Cell Numbers During Aging
Abstract
To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequency of cobblestone area-forming cells (CAFC) day-35 in DBA fetal liver was twofold to threefold higher than in B6 mice, and by late gestation, the total stem cell number was nearly as large as that of young DBA adults. Following a further ≈50% increase in stem cells between 6 weeks and 1 year of age, numbers in old DBA mice dropped precipitously between 12 and 20 months of age. In marked contrast, this stem cell population in B6 mice increased at a constant rate from late gestation to 20 months of age with no signs of abatement. Throughout development an inverse correlation was observed between stem cell numbers and the percentage of cells in S-phase. Because a strong genetic component contributed to the changes in stem cell numbers during aging, we quantified stem cells of 20-month old BXD recombinant inbred (RI) mice, derived from B6 and DBA progenitor strains, thus permitting detailed interstrain genetic analysis. For each BXD strain we calculated the stem cell increase or decrease as mice aged from 2 to 20 months. Net changes in CAFC-day 35 numbers among BXD strains ranged from an ≈10-fold decrease to an ≈10-fold increase. A genome-wide search for loci associated with this quantitative trait was performed. Several loci contribute to the trait—putative loci map to chromosomes X, 2, and 14. We conclude that stem cell numbers fluctuate widely during aging and that this has a strong genetic basis.
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Hematopoietic stem cells show several age-related changes, including impaired adherence to stromal cells and, in some mouse strains and elderly humans, an increased number.
“HSCs exhibit multiple age-related changes that include impaired adherence to stromal cells and, in some strains of mice (15,16) and elderly humans (17), an increase in number.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [15]
As humans age, they typically experience an increase in total phenotypic HSC numbers as the cell pool grows with time.
“As humans age, they typically experience an increase in total phenotypic HSC numbers as the cell pool grows with time (de Haan and Van Zant, 1999; Pang et al., 2011; Sudo et al., 2000).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as de Haan and Van Zant, 1999
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- Authors
- de Haan, G., & Van Zant, G.
- Affiliations
- From the Blood and Marrow Transplant Program, Division of Hematology/Oncology, University of Kentucky, Markey Cancer Center, Lexington, KY; and the Department of Physiological Chemistry, University of Groningen, Groningen, the Netherlands.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1999-05-15
- Volume
- 93
- Issue
- 10
- Pages
- 3294-3301
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2291689896
- Cited by
- 208
- References
- 56
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 8 · 2013: 6 · 2012: 10
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cells, aging, cobblestone area-forming cells, cell cycle, S phase, fetal liver, developmental stages, BXD recombinant inbred mice, genetic loci, quantitative trait loci, C57BL/6 mice, DBA/2 mice, strain differences
- MeSH terms
- Aging, Animals, Cell Cycle, Chromosome Mapping, Female, Embryonic and Fetal Development, Hematopoietic Stem Cells, Genetic Linkage, Liver, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Inbred Strains, Recombination, Genetic, Species Specificity, S Phase, Mice
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