Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
Open accessAbstract
We investigate the in vivo patterns of stem cell divisions in the human hematopoietic system throughout life. In particular, we analyze the shape of telomere length distributions underlying stem cell behavior within individuals. Our mathematical model shows that these distributions contain a fingerprint of the progressive telomere loss and the fraction of symmetric cell proliferations. Our predictions are tested against measured telomere length distributions in humans across all ages, collected from lymphocyte and granulocyte sorted telomere length data of 356 healthy individuals, including 47 cord blood and 28 bone marrow samples. We find an increasing stem cell pool during childhood and adolescence and an approximately maintained stem cell population in adults. Furthermore, our method is able to detect individual differences from a single tissue sample, i.e. a single snapshot. Prospectively, this allows us to compare cell proliferation between individuals and identify abnormal stem cell dynamics, which affects the risk of stem cell related diseases.
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The size of the HSC compartment changes dramatically during development and considerably increases in the transition into adulthood.
“The size of the HSC compartment also changes dramatically during development, and considerably increases in the transition into adulthood (Ganuza et al., 2017; Werner et al., 2015).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Werner et al., 2015
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References 60 · Cited by 95
- Authors
- Werner, B., Beier, F., Hummel, S., Balabanov, S., Lassay, L., Orlikowsky, T., Dingli, D., Brümmendorf, T. H., & Traulsen, A.
- Affiliations
- Max Planck Institute for Evolutionary Biology (DE)
- Universitätsklinikum Aachen (DE)
- University Hospital Zurich (CH)
- Mayo Clinic (US)
- Corresponding author
- Werner, Benjamin
- Traulsen, Arne
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-10-15
- Volume
- 4
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4744200
- OpenAlex
- W2230235941
- Cited by
- 95
- References
- 60
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 11 · 2023: 11 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 7 · 2018: 11 · 2017: 10 · 2016: 8
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Max Planck Digital Library (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- RWTH Aachen University
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- hematopoietic stem cells, telomere length distribution, stem cell division, symmetric cell division, telomere shortening, mathematical modeling, lymphocytes, granulocytes, umbilical cord blood, bone marrow, individual differences, aging
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cytological Techniques, Granulocytes, Hematopoietic Stem Cells, Humans, Infant, Infant, Newborn, Lymphocytes, Middle Aged, Models, Theoretical, Prospective Studies, Telomere, Cell Proliferation, Young Adult, Healthy Volunteers
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