Cited by 259Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchBlood disorders and treatments

The replication rate of human hematopoietic stem cells in vivo

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Catlin, Sandra N., Busque, Lambert, Gale, Rosemary E., Guttorp, Peter, Abkowitz, Janis L.·2011·Blood

Abstract

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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Crossref · 10.1182/blood-2010-08-303537

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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
Published
2011-04-28
Volume
117
Issue
17
Pages
4460-4466
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
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
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
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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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