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Asymmetry in erythroid-myeloid differentiation switch and the role of timing in a binary cell-fate decision.

Alagha, A; Zaikin, A; (2013) Asymmetry in erythroid-myeloid differentiation switch and the role of timing in a binary cell-fate decision. Frontiers in Immunology , 4 , Article 426. 10.3389/fimmu.2013.00426. Green open access

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Abstract

GATA1-PU.1 genetic switch is a paradigmatic genetic switch that governs the differentiation of progenitor cells into two different fates, erythroid and myeloid fates. In terms of dynamical model representation of these fates or lineages corresponds to stable attractor and choosing between the attractors. Small asymmetries and stochasticity intrinsically present in all genetic switches lead to the effect of delayed bifurcation which will change the differentiation result according to the timing of the process and affect the proportion of erythroid versus myeloid cells. We consider the differentiation bifurcation scenario in which there is a symmetry-breaking in the bifurcation diagrams as a result of asymmetry in external signaling. We show that the decision between two alternative cell fates in this structurally symmetric decision circuit can be biased depending on the speed at which the system is forced to go through the decision point. The parameter sweeping speed can also reduce the effect of asymmetry and produce symmetric choice between attractors, or convert the favorable attractor. This conversion may have important contributions to the immune system when the bias is in favor of the attractor which gives rise to non-immune cells.

Type: Article
Title: Asymmetry in erythroid-myeloid differentiation switch and the role of timing in a binary cell-fate decision.
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2013.00426
Publisher version: http://dx.doi.org/10.3389/fimmu.2013.00426
Language: English
Additional information: © 2013 Alagha and Zaikin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. PMCID: PMC3851994
Keywords: GATA1-PU.1 switch, differentiation, immune cells, pluripotent cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/1417473
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