Towards an understanding of lineage specification in hematopoietic stem cells: a mathematical model for the interaction of transcription factors GATA-1 and PU.1

Journal of Theoretical Biology
Ingo Roeder, Ingmar Glauche

Abstract

In addition to their self-renewal capabilities, hematopoietic stem cells guarantee the continuous supply of fully differentiated, functional cells of various types in the peripheral blood. The process which controls differentiation into the different lineages of the hematopoietic system (erythroid, myeloid, lymphoid) is referred to as lineage specification. It requires a potentially multi-step decision sequence which determines the fate of the cells and their successors. It is generally accepted that lineage specification is regulated by a complex system of interacting transcription factors. However, the underlying principles controlling this regulation are currently unknown. Here, we propose a simple quantitative model describing the interaction of two transcription factors. This model is motivated by experimental observations on the transcription factors GATA-1 and PU.1, both known to act as key regulators and potential antagonists in the erythroid vs. myeloid differentiation processes of hematopoietic progenitor cells. We demonstrate the ability of the model to account for the observed switching behavior of a transition from a state of low expression of both factors (undifferentiated state) to the dominance of one factor (di...Continue Reading

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