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A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells
Open accessAbstract
Whether hematopoietic stem cells (HSCs) change with aging has been controversial. Previously, we showed that the HSC compartment in young mice consists of distinct subsets, each with predetermined self-renewal and differentiation behavior. Three classes of HSCs can be distinguished based on their differentiation programs: lymphoid biased, balanced, and myeloid biased. We now show that aging causes a marked shift in the representation of these HSC subsets. A clonal analysis of repopulating HSCs demonstrates that lymphoid-biased HSCs are lost and long-lived myeloid-biased HSCs accumulate in the aged. Myeloid-biased HSCs from young and aged sources behave similarly in all aspects tested. This indicates that aging does not change individual HSCs. Rather, aging changes the clonal composition of the HSC compartment. We show further that genetic factors contribute to the age-related changes of the HSC subsets. In comparison with B6 mice, aged D2 mice show a more pronounced shift toward myeloid-biased HSCs with a corresponding reduction in the number of both T- and B-cell precursors. This suggests that low levels of lymphocytes in the blood can be a marker for HSC aging. The loss of lymphoid-biased HSCs may contribute to the impaired immune response to infectious diseases and cancers in the aged.
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In the citing paper
“it is now appreciated that the number of lymphoid-biased stem cells declines with age concomitant with an increase in myeloid-biased HSCs (19).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [19]
In the citing paper
“in aged mice that display an overall increase in HSC pool size”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
In the citing paper
“the functional heterogeneity of the HSC population increases with age.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
In the citing paper
“individual HSCs behave very differently.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
In the citing paper
“mice in which blood cell production is derived from even a single stem cell, are not necessarily prone to develop leukemia.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
In the citing paper
“examination of donor-derived reconstitution from old HSCs was significantly lower compared to the young with a marked myeloid bias lineage output”
From Quiescent Hematopoietic Stem Cells Accumulate DNA Damage during Aging that Is Repaired upon Entry into Cell Cycle (2014) · cites this paper as Cho et al., 2008
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Metadata
- Authors
- Cho, R. H., Sieburg, H. B., & Muller-Sieburg, C. E.
- Affiliations
- Sidney Kimmel Cancer Center (US)
- Sidney Kimmel Cancer Center, San Diego, CA
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-06-15
- Volume
- 111
- Issue
- 12
- Pages
- 5553-5561
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2424153
- OpenAlex
- W1974139477
- Cited by
- 377
- References
- 62
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 23 · 2023: 27 · 2022: 18 · 2021: 19 · 2020: 26 · 2019: 22 · 2018: 16 · 2017: 19 · 2016: 24 · 2015: 20 · 2014: 22 · 2013: 31 · 2012: 23
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Miami
- National Institutes of Health
- National Institute on Aging (R01AG023197, AG023197)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK048015, R01DK048015, R56DK048015)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cells, aging, clonal composition, self-renewal, clonal analysis, T cell precursors, B cell precursors, genetic factors, C57BL/6 mice, immunosenescence
- MeSH terms
- Aging, Animals, B-Lymphocytes, Blood, Clone Cells, Genetic Markers, Hematopoietic Stem Cells, Lymphocytes, Mice, Inbred Strains, Mice, Transgenic, T-Lymphocytes, Thymus Gland, Cellular Senescence, Cell Lineage, Mice, Congenic, Myeloid Cells, Mice
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