The DOI matches its Crossref record; 61 of the 62 references it cites were found in a registry or an index.
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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Citations
Cites
Cell intrinsic alterations underlie hematopoietic stem cell aging
Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503280102 · Cited by 1,152 · cited 1×
“For example, aged HSCs may have a reduced ability to home to the bone marrow (BM),(5,6) an altered cell surface phenotype,(5,7) may cycle more rapidly,(5) produce more myeloid cells,(5-8) and have a different gene expression program than their young counterparts.(9,10) HSCs from aged environments may have slightly les…”
BackgroundDeficiencies in DNA damage repair limit the function of haematopoietic stem cells with age
Rossi, D. J., Bryder, D., Seita, J., Nussenzweig, A., Hoeijmakers, J., & Weissman, I. L. (2007) · Nature · doi:10.1038/nature05862 · Cited by 1,115
Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106
The aging of hematopoietic stem cells
Morrison, S. J., Wandycz, A. M., Akashi, K., Globerson, A., & Weissman, I. L. (1996) · Nature Medicine · doi:10.1038/nm0996-1011 · Cited by 853
Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation
Chambers, S. M., Shaw, C. A., Gatza, C. E., Fisk, C. J., Donehower, L. A., & Goodell, M. A. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050201 · Cited by 806
Age-Associated Characteristics of Murine Hematopoietic Stem Cells
Sudo, K., Ema, H., Morita, Y., & Nakauchi, H. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.9.1273 · Cited by 722
Long-Term Propagation of Distinct Hematopoietic Differentiation Programs In Vivo
Dykstra, B. J., Kent, D. G., Bowie, M. B., McCaffrey, L., Hamilton, M. J., Lyons, K., Lee, S.-J., Brinkman, R. R., & Eaves, C. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.015 · Cited by 632
Clonal and systemic analysis of long-term hematopoiesis in the mouse.Preprint
Jordan, C. T., & Lemischka, I. R. (1990) · Genes & Development · doi:10.1101/gad.4.2.220 · Cited by 550
DNA repair is limiting for haematopoietic stem cells during ageing
Nijnik, A., Woodbine, L., Marchetti, C., Dawson, S., Lambe, T., Liu, C., Rodrigues, N. P., Crockford, T. L., Cabuy, E., Vindigni, A., et al. (2007) · Nature · doi:10.1038/nature05875 · Cited by 518
Szilvassy, S. J., Humphries, R. K., Lansdorp, P. M., Eaves, A. C., & Eaves, C. J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.22.8736 · Cited by 450
Research works printed but not linked: 2
- Graf, 2007, Two lineages of hematopoietic stem cells identified by differences in lineage priming. [Abstract.], Exp Hematol, 35
- Lichtman, 2001, Hamatology in the Aged
Cited by
Sorted by citations
Age-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116110108 · Cited by 991
Haematopoietic stem cell activity and interactions with the niche
Pinho, S., & Frenette, P. S. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0103-9 · Cited by 1,064
Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793
Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D., & Rossi, D. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000834107 · Cited by 711
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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