Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

Blog Article

The life-long supply of blood cells depends on the long-term function of hematopoietic stem cells (HSCs).HSCs are functionally defined by their multi-potency and self-renewal capacity.Because of their self-renewal capacity, HSCs were thought to have indefinite lifespans.However, there is increasing evidence that genetically identical HSCs differ in lifespan and that the lifespan of a HSC is predetermined and HSC-intrinsic.

Lifespan is here defined as the time a HSC gives rise to Custom Product all mature blood cells.This raises the intriguing question: what controls the lifespan of HSCs within the same animal, exposed to the same environment? We present here a new model based on reliability theory to account for the diversity of lifespans of HSCs.Using clonal repopulation experiments and computational-mathematical modeling, we tested how small-scale, molecular level, failures are dissipated at the HSC population level.We found that the best fit of the experimental data is provided by a model, where the repopulation failure kinetics of each HSC are largely anti-persistent, or mean-reverting, processes.

Thus, failure rates repeatedly increase during population-wide division 4 Piece Home Office events and are counteracted and decreased by repair processes.In the long-run, a crossover from anti-persistent to persistent behavior occurs.The cross-over is due to a slow increase in the mean failure rate of self-renewal and leads to rapid clonal extinction.This suggests that the repair capacity of HSCs is self-limiting.

Furthermore, we show that the lifespan of each HSC depends on the amplitudes and frequencies of fluctuations in the failure rate kinetics.Shorter and longer lived HSCs differ significantly in their pre-programmed ability to dissipate perturbations.A likely interpretation of these findings is that the lifespan of HSCs is determined by preprogrammed differences in repair capacity.