Biology – Quantitative Biology – Molecular Networks
Scientific paper
2006-01-18
Biology
Quantitative Biology
Molecular Networks
27 pages, 8 figures, accepted for publication in Journal of Theoretical Biology
Scientific paper
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 (differentiated state). Depending on the parameter choice, the model predicts two different possibilities to explain the experimentally suggested, stem cell characterizing priming state of low level co-expression. Whereas increasing transcription rates are sufficient to induce differentiation in one scenario, an additional system perturbation (by stochastic fluctuations or directed impulses) of transcription factor levels is required in the other case.
Glauche Ingmar
Roeder Ingo
No associations
LandOfFree
Towards an understanding of lineage specification in hematopoietic stem cells: A mathematical model for the interaction of transcription factors GATA-1 and PU.1 does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.
If you have personal experience with Towards an understanding of lineage specification in hematopoietic stem cells: A mathematical model for the interaction of transcription factors GATA-1 and PU.1, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Towards an understanding of lineage specification in hematopoietic stem cells: A mathematical model for the interaction of transcription factors GATA-1 and PU.1 will most certainly appreciate the feedback.
Profile ID: LFWR-SCP-O-594496