Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions

  1. Benjamin Werner  Is a corresponding author
  2. Fabian Beier
  3. Sebastian Hummel
  4. Stefan Balabanov
  5. Lisa Lassay
  6. Thorsten Orlikowsky
  7. David Dingli
  8. Tim H Brümmendorf
  9. Arne Traulsen
  1. Max Planck Institute for Evolutionary Biology, Germany
  2. Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Germany
  3. University Hospital of Zürich, Switzerland
  4. 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.

Article and author information

Author details

  1. Benjamin Werner

    Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
    For correspondence
    werner@evolbio.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
  2. Fabian Beier

    Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Sebastian Hummel

    Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Stefan Balabanov

    Division of Hematology, University Hospital of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Lisa Lassay

    Department of Pediatrics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Thorsten Orlikowsky

    Department of Pediatrics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. David Dingli

    Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Tim H Brümmendorf

    Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Arne Traulsen

    Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
    Competing interests
    The authors declare that no competing interests exist.

Ethics

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.

Reviewing Editor

  1. Frank Jülicher, Max Planck Institute for the Physics of Complex Systems, Germany

Publication history

  1. Received: May 13, 2015
  2. Accepted: October 14, 2015
  3. Accepted Manuscript published: October 15, 2015 (version 1)
  4. Version of Record published: January 27, 2016 (version 2)

Copyright

© 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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  1. Benjamin Werner
  2. Fabian Beier
  3. Sebastian Hummel
  4. Stefan Balabanov
  5. Lisa Lassay
  6. Thorsten Orlikowsky
  7. David Dingli
  8. Tim H Brümmendorf
  9. Arne Traulsen
(2015)
Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
eLife 4:e08687.
https://doi.org/10.7554/eLife.08687
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