Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion
Open accessAbstract
Aging of the hematopoietic stem cell compartment is believed to contribute to the onset of a variety of age-dependent blood cell pathophysiologies. Mechanistic drivers of hematopoietic stem cell (HSC) aging include DNA damage accumulation and induction of tumor suppressor pathways that combine to reduce the regenerative capacity of aged HSCs. Such mechanisms do not however account for the change in lymphoid and myeloid lineage potential characteristic of HSC aging, which is believed to be central to the decline of immune competence and predisposition to myelogenous diseases in the elderly. Here we have prospectively isolated functionally distinct HSC clonal subtypes, based on cell surface phenotype, bearing intrinsically different capacities to differentiate toward lymphoid and myeloid effector cells mediated by quantitative differences in lineage priming. Finally, we present data supporting a model in which clonal expansion of a class of intrinsically myeloid-biased HSCs with robust self-renewal potential is a central component of hematopoietic aging.
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The functional heterogeneity of the HSC population rises with age.
“the functional heterogeneity of the HSC population increases with age.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [17]
Aged mice have an overall larger HSC pool.
“in aged mice that display an overall increase in HSC pool size”
From Aging of hematopoietic stem cells (2018) · cites this paper as [17]
Individual HSCs in aged mice behave very differently from one another.
“individual HSCs behave very differently.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [17]
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References 34 · Cited by 711
- Authors
- Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D., & Rossi, D. J.
- Affiliations
- Boston Children's Hospital (US)
- Washington University in St. Louis (US)
- Linköping University (SE)
- Stanford Medicine (US)
- Lund University (SE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-03-23
- Volume
- 107
- Issue
- 12
- Pages
- 5465-5470
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2851806
- OpenAlex
- W2159082795
- Cited by
- 711
- References
- 34
- Citations by year
- 2026: 45 · 2025: 42 · 2024: 37 · 2023: 48 · 2022: 53 · 2021: 57 · 2020: 38 · 2019: 43 · 2018: 54 · 2017: 34 · 2016: 55 · 2015: 36 · 2014: 40 · 2013: 47 · 2012: 41
- FWCI
- 25.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Cancerfonden
- Crafoordska Stiftelsen
- Lunds Universitet
- Harvard Stem Cell Institute
- Medical Research Council
- National Cancer Institute (R01CA086065)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK078318)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- hematopoietic stem cells, HSC aging, clonal expansion, lineage priming, self-renewal, immunosenescence, DNA damage, tumor suppressor pathways
- MeSH terms
- Signaling Lymphocytic Activation Molecule Family Member 1, Aging, Animals, Hematopoiesis, Hematopoietic Stem Cells, Mice, Inbred C57BL, Models, Biological, Receptors, Cell Surface, Antigens, CD, Hematopoietic Stem Cell Transplantation, Myelopoiesis, Mice
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