Mathematical modelling of stem cell differentiation: the PU.1-GATA-1 interaction

Abstract

The transcription factors PU.1 and GATA-1 are known to be important in the development of blood progenitor cells. Specifically they are thought to regulate the differentiation of progenitor cells into the granulocyte/macrophage lineage and the erythrocyte/megakaryocite lineage. While several mathematical models have been proposed to investigate the interaction between the transcription factors in recent years, there is still debate about the nature of the progenitor state in the dynamical system, and whether the existing models adequately capture new knowledge about the interactions gleaned from experimental data. Further, the models utilise different formalisms to represent the genetic regulation, and it appears that the resulting dynamical system depends upon which formalism is adopted. In this paper we analyse the four existing models, and propose an alternative model which is shown to demonstrate a rich variety of dynamical systems behaviours found across the existing models, including both bistability and tristability required for modelling the undifferentiated progenitors.