Despite rapid advances in experimental cell biology, the in vivo behavior ofhematopoietic stem cells (HSC) cannot be directly observed and measured.Previously we modeled feline hematopoiesis using a two-compartment hiddenMarkov process that had birth and emigration events in the first compartment.Here we perform Bayesian statistical inference on models which contain twoadditional events in the first compartment in order to determine if HSC fatedecisions are linked to cell division or occur independently. Pareto OptimalModel Assessment approach is used to cross check the estimates from Bayesianinference. Our results show that HSC must divide symmetrically (i.e., producetwo HSC daughter cells) in order to maintain hematopoiesis. We then demonstratethat the augmented model that adds asymmetric division events provides a betterfit to the competitive transplantation data, and we thus provide evidence thatHSC fate determination in vivo occurs both in association with cell divisionand at a separate point in time. Last we show that assuming each cat has aunique set of parameters leads to either a significant decrease or anonsignificant increase in model fit, suggesting that the kinetic parametersfor HSC are not unique attributes of individual animals, but shared within aspecies.
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