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

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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

DOI 10.1182/blood-2010-08-303537PMC PMC3099568

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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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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)
ORCID: Busque, Lambert
Gale, Rosemary E.
Guttorp, Peter
Abkowitz, Janis L.
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
DOI: 10.1182/blood-2010-08-303537
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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The replication rate of human hematopoietic stem cells in vivo

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