Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
- Max Planck Institute for Evolutionary Biology, Germany
- Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Germany
- University Hospital of Zürich, Switzerland
- Mayo Clinic, United States
Abstract
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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Human subjects: All samples and the approval for publication were taken with informed consent of all patients at the University Hospital Aachen according to the guidelines and the approval of the ethics committees at the University Hospital Aachen.
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© 2015, Werner et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
eLife 4:e08687.
https://doi.org/10.7554/eLife.08687
