Combined Biological and Modeling Approach of Hematopoiesis: From Native to Stressed Erythropoiesis

Abstract

We developed here a new mathematical modelling approach which reconciliates native and stress hematopoiesis, focused on hematopoietic stem and progenitor compartments. We first proposed an erythropoiesis model leaning on a minimum of 6 cell-amplification compartments, able to reproduce native erythropoiesis. A phenylhydrazine-induced hemolytic stress was next applied, and in vivo data were used to estimate model parameters through an optimized algorithm and integrated regulatory processes. A reduction of all stem cell compartments was observed, due to a drastic differentiation without proliferation during 7 days, followed by a huge proliferation in all compartments including long-term hematopoietic stem cells, before returning to normal values. The 6-compartment model applied to stress erythropoiesis was complexified by integrating regulatory processes. Thus, regulation of hematopoiesis appears dispensable during native hematopoiesis but mandatory for stress hematopoiesis. In conclusion this multi-step and time-dependent model of immature hematopoiesis opens new opportunities to understand development of normal or pathological hematopoiesis.