Mathematical Analysis of Cytokine-Induced Differentiation of Granulocyte-Monocyte Progenitor Cells

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dc.contributor.authorWeston, Bronson R.en
dc.contributor.authorLi, Liwuen
dc.contributor.authorTyson, John J.en
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2019-08-29T12:25:41Zen
dc.date.available2019-08-29T12:25:41Zen
dc.date.issued2018-09-18en
dc.description.abstractGranulocyte-monocyte progenitor (GMP) cells play a vital role in the immune system by maturing into a variety of white blood cells, including neutrophils and macrophages, depending on exposure to cytokines such as various types of colony stimulating factors (CSF). Granulocyte-CSF (G-CSF) induces granulopoiesis and macrophage-CSF (M-CSF) induces monopoiesis, while granulocyte/macrophage-CSF (GM-CSF) favors monocytic and granulocytic differentiation at low and high concentrations, respectively. Although these differentiation pathways are well documented, the mechanisms behind the diverse behavioral responses of GMP cells to CSFs are not well understood. In this paper, we propose a mechanism of interacting CSF-receptors and transcription factors that control GMP differentiation, convert the mechanism into a set of differential equations, and explore the properties of this mathematical model using dynamical systems theory. Our model reproduces numerous experimental observations of GMP cell differentiation in response to varying dosages of G-CSF, M-CSF, and GM-CSF. In particular, we are able to reproduce the concentration-dependent behavior of GM-CSF induced differentiation, and propose a mechanism driving this behavior. In addition, we explore the differentiation of a fourth phenotype, monocytic myeloid-derived suppressor cells (M-MDSC), showing how they might fit into the classical pathways of GMP differentiation and how progenitor cells can be primed for M-MDSC differentiation. Finally, we use the model to make novel predictions that can be explored by future experimental studies.en
dc.description.sponsorshipThis work was partly funded through NIH grant HL115835 to LL.en
dc.format.extent21 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationWeston BR, Li L and Tyson JJ (2018) Mathematical Analysis of Cytokine-Induced Differentiation of Granulocyte-Monocyte Progenitor Cells. Front. Immunol. 9:2048. doi: 10.3389/fimmu.2018.02048en
dc.identifier.doihttps://doi.org/10.3389/fimmu.2018.02048en
dc.identifier.urihttp://hdl.handle.net/10919/93292en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectgranulopoiesisen
dc.subjectmonopoiesisen
dc.subjectdifferentiationen
dc.subjectcytokinesen
dc.subjectmathematical modelingen
dc.subjecttemporal dynamicsen
dc.subjectmonocytic myeloid-derived suppressor cellsen
dc.titleMathematical Analysis of Cytokine-Induced Differentiation of Granulocyte-Monocyte Progenitor Cellsen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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