The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Open accessAbstract
In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.
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In the citing paper
“Although the number of peripheral B cells decreases with age, a more pronounced decrease of B cells in AD was observed, suggesting that ongoing disease may exacerbate ageing effects [88,89].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [89]
In the citing paper
“This shift has been correlated with increased expression of myeloid lineage genes and downregulation of those specifying a lymphoid lineage fate (11,17).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [17]
In the citing paper
“From an immunologic perspective, the most profound effect of stem cell aging in both mice (11,18) and humans (17) is a decreased capacity to produce lymphocytes and an increase in myeloid potential.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [17]
In the citing paper
“The age-related increase in expression of myeloid lineage genes in the studies noted above (11,17) likely resulted from the accumulation of myeloid-biased HSCs, as these analyses were performed on unseparated pools of HSCs.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [17]
In the citing paper
“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 [17]
In the citing paper
“an age-dependent increase in the frequency of putative stem cells, coinciding with impaired functionality and reduced lymphoid potential, has also been in the human system.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [28]
In the citing paper
“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 Pang et al., 2011
Citations
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“Notably, the results from our functional analysis and gene expression profiling of young and elderly human HSC significantly parallel the data we and others have generated on young and elderly mouse HSC (2, 6, 36).”
BackgroundResultSelf-citationIsolation of a candidate human hematopoietic stem-cell population.
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Variation in cancer risk among tissues can be explained by the number of stem cell divisions
Tomasetti, C., & Vogelstein, B. (2015) · Science · doi:10.1126/science.1260825 · Cited by 1,927
Single-cell RNA sequencing to explore immune cell heterogeneity
Papalexi, E., & Satija, R. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.76 · Cited by 1,806
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443
“This leads to a reduction in the number of precursors for T and B cells with increasing age.(108,109) Taken together, with aging, the number of HSCs increases, while their function including self-renewal and clonogenicity, decreases.”
BackgroundMass Cytometry: Single Cells, Many Features
Spitzer, M. H., & Nolan, G. P. (2016) · Cell · doi:10.1016/j.cell.2016.04.019 · Cited by 1,199
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
Metadata
- Authors
- Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L.
- Affiliations
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Department of Internal Medicine, Division of Hematology, and
- Harvard University (US)
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-11-28
- Volume
- 108
- Issue
- 50
- Pages
- 20012-20017
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3250139
- OpenAlex
- W2028815852
- Cited by
- 991
- References
- 49
- Citations by year
- 2026: 79 · 2025: 79 · 2024: 93 · 2023: 87 · 2022: 85 · 2021: 91 · 2020: 83 · 2019: 55 · 2018: 59 · 2017: 54 · 2016: 51 · 2015: 49 · 2014: 63 · 2013: 36 · 2012: 26
- FWCI
- 27.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG029124)
- National Cancer Institute (R01CA086065, K99CA151673)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- hematopoietic stem cells, aging, bone marrow, myeloid differentiation, HSC quiescence, hematopoietic progenitor cells, gene expression profiling, immunophenotype, myeloid neoplasms
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Animals, Bone Marrow Cells, Cell Count, Cell Differentiation, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Middle Aged, Cell Lineage, Gene Expression Profiling, Myeloid Cells, Mice, Young Adult
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