Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
Benjamin Werner,
Fabian Beier,
Sebastian Hummel,
Stefan Balabanov,
Lisa Lassay,
Thorsten Orlikowsky,
David Dingli,
Tim H Brümmendorf,
Arne Traulsen
Affiliations
Benjamin Werner
Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
Fabian Beier
Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
Sebastian Hummel
Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
Stefan Balabanov
Division of Hematology, University Hospital of Zürich, Zürich, Switzerland
Lisa Lassay
Department of Pediatrics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
Thorsten Orlikowsky
Department of Pediatrics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
David Dingli
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, United States; Department of Molecular Medicine, Mayo Clinic, Rochester, United States
Tim H Brümmendorf
Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany
Arne Traulsen
Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
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.