Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Simple principles can explain the in vivo population dynamics of tissue specific stem cells
Benjamin Werner

Last modified: 2014-03-31

Abstract


Tissue homeostasis is impelled by the occasional differentiation of infrequently dividing multipotent stem cells. These cells are involved in the formation, maintenance, renewal, and aging of tissues and numerous cancers emerge from aberrant cell proliferation. Although many aspects of the genetic and molecular mechanisms of stem cell regulation are known, the overalldynamics of stem cell populations in vivo is predominantly  obtained from repopulation and tracing experiments in animal models and remains only vaguely understood in humans.Here we show that the intrinsic shortening of telomeres, the noncoding ends of chromosomes, allows quantitative predictions for the dynamics of hematopoietic stem cells. Age related patterns in telomere length distributions, inferred from lymphocyte and granulocyte samples in humans, are explained by exact solutions of our mathematical model. We show that an interplay of asymmetric and symmetric cell divisions leads to a continued slow increase in stem cell numbers with age, causing a pronounced loss in telomere length through adolescence. Our model can identify basic stem cell properties in individuals and might serve as an additional tool towards personalized medicine.

Keywords


Telomeres, stem cells, cancer