dorsal/arxiv
View SchemaTowards an understanding of lineage specification in hematopoietic stem cells: A mathematical model for the interaction of transcription factors GATA-1 and PU.1
| Authors | Ingo Roeder, Ingmar Glauche |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0601025 |
| URL | https://arxiv.org/abs/q-bio/0601025 |
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 (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.
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"abstract": "In addition to their self-renewal capabilities, hematopoietic stem cells\nguarantee the continuous supply of fully differentiated, functional cells of\nvarious types in the peripheral blood. The process which controls\ndifferentiation into the different lineages of the hematopoietic system\n(erythroid, myeloid, lymphoid) is referred to as lineage specification. It\nrequires a potentially multi-step decision sequence which determines the fate\nof the cells and their successors. It is generally accepted that lineage\nspecification is regulated by a complex system of interacting transcription\nfactors. However, the underlying principles controlling this regulation are\ncurrently unknown.\n Here, we propose a simple quantitative model describing the interaction of\ntwo transcription factors. This model is motivated by experimental observations\non the transcription factors GATA-1 and PU.1, both known to act as key\nregulators and potential antagonists in the erythroid vs. myeloid\ndifferentiation processes of hematopoietic progenitor cells. We demonstrate the\nability of the model to account for the observed switching behavior of a\ntransition from a state of low expression of both factors (undifferentiated\nstate) to the dominance of one factor (differentiated state). Depending on the\nparameter choice, the model predicts two different possibilities to explain the\nexperimentally suggested, stem cell characterizing priming state of low level\nco-expression. Whereas increasing transcription rates are sufficient to induce\ndifferentiation in one scenario, an additional system perturbation (by\nstochastic fluctuations or directed impulses) of transcription factor levels is\nrequired in the other case.",
"arxiv_id": "q-bio/0601025",
"authors": [
"Ingo Roeder",
"Ingmar Glauche"
],
"categories": [
"q-bio.MN",
"q-bio.QM"
],
"title": "Towards an understanding of lineage specification in hematopoietic stem cells: A mathematical model for the interaction of transcription factors GATA-1 and PU.1",
"url": "https://arxiv.org/abs/q-bio/0601025"
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