摘要：SummaryWe have reconciled steady-state and stress hematopoiesis in a single mathematical model based on murinein vivoexperiments and with a focus on hematopoietic stem and progenitor cells. A phenylhydrazine stress was first applied to mice. A reduced cell number in each progenitor compartment was evidenced during the next 7 days through a drastic level of differentiation without proliferation, followed by a huge proliferative response in all compartments including long-term hematopoietic stem cells, before a return to normal levels. Data analysis led to the addition to the 6-compartment model, of time-dependent regulation that depended indirectly on the compartment sizes. The resulting model was finely calibrated using a stochastic optimization algorithm and could reproduce biological datain silicowhen applied to different stress conditions (bleeding, chemotherapy, HSC depletion). In conclusion, our multi-step and time-dependent model of immature hematopoiesis provides new avenues to a better understanding of both normal and pathological hematopoiesis.Graphical abstractDisplay OmittedHighlights•We describe a new 6-compartment time-dependent regulated model of hematopoiesis•Biological data under steady state and stress and cell dynamics were used•Modeling is able to recapitulate effects from chemotherapy, bleeding, or HSC depletionCell biology; Stem cells research;In silicobiology
