title: Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions.
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.
authors.affiliation: Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Werner
authors.affiliation: Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Beier
authors.affiliation: Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hummel
authors.affiliation: Division of Hematology, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Balabanov
authors.affiliation: Department of Pediatrics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lassay
authors.affiliation: Department of Pediatrics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Orlikowsky
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, United States.|Department of Molecular Medicine, Mayo Clinic, Rochester, United States.
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.affiliation: Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Traulsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D003584:Cytological Techniques; D006098:Granulocytes / Q000166:cytology / Q000502:physiology; D064368:Healthy Volunteers; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D008875:Middle Aged; D008962:Models, Theoretical; D011446:Prospective Studies; D016615:Telomere; D055815:Young Adult
keywords: computational biology; developmental biology; hematopoiesis; human; mathematical modelling; personalised medicine; self renewal; stem cells; systems biology; telomere length distribution