Hematopoietic stem cells count and remember self-renewal divisions
Open accessAbstract
The ability of cells to count and remember their divisions could underlie many alterations that occur during development, aging, and disease. We tracked the cumulative divisional history of slow-cycling hematopoietic stem cells (HSCs) throughout adult life. This revealed a fraction of rarely dividing HSCs that contained all the long-term HSC (LT-HSC) activity within the aging HSC compartment. During adult life, this population asynchronously completes four traceable symmetric self-renewal divisions to expand its size before entering a state of dormancy. We show that the mechanism of expansion involves progressively lengthening periods between cell divisions, with long-term regenerative potential lost upon a fifth division. Our data also show that age-related phenotypic changes within the HSC compartment are divisional history dependent. These results suggest that HSCs accumulate discrete memory stages over their divisional history and provide evidence for the role of cellular memory in HSC aging.
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In mice, the most primitive HSCs divide about once every four months.
“In mice, the most primitive HSC are believed to cycle only once every ;4 months.23”
From Aging of hematopoietic stem cells (2018) · cites this paper as [23]
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- Authors
- Bernitz, J. M., Kim, H. S., MacArthur, B., Sieburg, H., & Moore, K.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University of Southampton (GB)
- Vaccine Research Institute of San Diego (US)
- Corresponding author
- Moore, Kateri
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 167
- Issue
- 5
- Pages
- 1296-1309.e10
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5115957
- OpenAlex
- W2552591666
- Cited by
- 285
- References
- 46
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 21 · 2023: 28 · 2022: 30 · 2021: 41 · 2020: 38 · 2019: 33 · 2018: 39 · 2017: 18 · 2016: 2
- FWCI
- 29.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Funders
- NIH (2R01HL58739, T32HD075735)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- hematopoietic stem cells, cellular memory, long-term HSCs, HSC aging, stem cell quiescence, regenerative capacity
- MeSH terms
- Aging, Animals, Bone Marrow Cells, Cell Cycle, Cell Division, Hematopoietic Stem Cells, Mice, Inbred C57BL, Bone Marrow Transplantation, Platelet Membrane Glycoprotein IIb, Mice
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