Leukocyte telomere dynamics and human hematopoietic stem cell kinetics during somatic growth.

A central question in stem cell research is knowing the frequency of human hematopoietic stem cells (HSC) replication in vivo. We have constructed a model that characterizes HSC kinetics and the relative sizes of the hematopoietic progenitor cell (HPC) and HSC pools from birth onward. The model capitalizes on leukocyte telomere length (LTL) data and body weight-gain charts from birth to the age of 20 years. The core premise of the model is that during human growth, LTL dynamics (birth LTL and age-dependent LTL shortening afterward) chronicle the expansions of the HSC and HPC pools. The model estimates that by the end of the first year of life, HSC have replicated approximately 17 times and they replicate approximately 2.5 times/year between the ages of 3 and 13 years. Subsequently, HSC replication slows considerably. In adults HSC replicate at a rate of approximately 0.6 times/year. In addition, the model predicts that newborns with small birth weight would have shorter LTL as adults and that women would have longer LTL than men. Our findings will be useful in bone marrow transplantations and might explain a body of clinical observations related to LTL distribution in the general population.