Cited by 991Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchAcute Myeloid Leukemia Research

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

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Abstract

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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Crossref · 10.1073/pnas.1116110108

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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
Published
2011-11-28
Volume
108
Issue
50
Pages
20012-20017
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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