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Elife. 2015 Oct 15;4. pii: e08687. doi: 10.7554/eLife.08687.

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

Author information

1
Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
2
Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
3
Division of Hematology, University Hospital of Zürich, Zürich, Switzerland.
4
Department of Pediatrics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
5
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, United States.
6
Department of Molecular Medicine, Mayo Clinic, Rochester, 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.

KEYWORDS:

computational biology; developmental biology; hematopoiesis; human; mathematical modelling; personalised medicine; self renewal; stem cells; systems biology; telomere length distribution

PMID:
26468615
PMCID:
PMC4744200
DOI:
10.7554/eLife.08687
[Indexed for MEDLINE]
Free PMC Article

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