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The replication rate of human hematopoietic stem cells in vivo
Open accessAbstract
Hematopoietic stem cells (HSCs) replicate (self-renew) to create 2 daughter cells with capabilities equivalent to their parent, as well as differentiate, and thus can both maintain and restore blood cell production. Cell labeling with division-sensitive markers and competitive transplantation studies have been used to estimate the replication rate of murine HSCs in vivo. However, these methods are not feasible in humans and surrogate assays are required. In this report, we analyze the changing ratio with age of maternal/paternal X-chromosome phenotypes in blood cells from females and infer that human HSCs replicate on average once every 40 weeks (range, 25-50 weeks). We then confirm this estimate with 2 independent approaches, use the estimate to simulate human hematopoiesis, and show that the simulations accurately reproduce marrow transplantation data. Our simulations also provide evidence that the number of human HSCs increases from birth until adolescence and then plateaus, and that the ratio of contributing to quiescent HSCs in humans significantly differs from mouse. In addition, they suggest that human marrow failure, such as the marrow failure that occurs after umbilical cord blood transplantation and with aplastic anemia, results from insufficient numbers of early progenitor cells, and not the absence of HSCs.
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“current estimates that there are approximately 10,000 HSCs in humans12”
From Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia (2015) · cites this paper as [12]
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Metadata
- Authors
- Catlin, S. N., Busque, L., Gale, R. E., Guttorp, P., & Abkowitz, J. L.
- Affiliations
- University of Nevada, Las Vegas (US)
- Hôpital Maisonneuve-Rosemont (CA)
- University College London (GB)
- Norwegian Computing Center (NO)
- University of Washington (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-04-28
- Volume
- 117
- Issue
- 17
- Pages
- 4460-4466
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3099568
- OpenAlex
- W2072193332
- Cited by
- 259
- References
- 48
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 20 · 2023: 14 · 2022: 18 · 2021: 28 · 2020: 22 · 2019: 17 · 2018: 18 · 2017: 19 · 2016: 15 · 2015: 11 · 2014: 16 · 2013: 18 · 2012: 12
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL046598, R01HL082933, R01-HL46598)
- National Center for Research Resources (UL1RR025014)
- 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 › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, HSC self-renewal, X chromosome inactivation, bone marrow transplantation, HSC quiescence, cord blood transplantation, aplastic anemia, bone marrow failure
- MeSH terms
- Bone Marrow Failure Disorders, Adolescent, Adult, Aging, Anemia, Aplastic, Animals, Bone Marrow Diseases, Cats, Cell Division, Child, Child, Preschool, Computer Simulation, Female, Hematopoiesis, Hematopoietic Stem Cells, Hemoglobinuria, Paroxysmal, Humans, Infant, Infant, Newborn, Models, Biological, Phenotype, Species Specificity, Stochastic Processes, Cord Blood Stem Cell Transplantation, X Chromosome Inactivation, Mice, Young Adult
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