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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Proliferation*
  • Child
  • Child, Preschool
  • Cytological Techniques
  • Granulocytes / cytology
  • Granulocytes / physiology
  • Healthy Volunteers
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Infant
  • Infant, Newborn
  • Lymphocytes / cytology
  • Lymphocytes / physiology
  • Middle Aged
  • Models, Theoretical
  • Prospective Studies
  • Telomere*
  • Young Adult

Grant support

No external funding was received for this work.