Mean-Independent Noise Control of Cell Fates via Intermediate States
Summary: Stochasticity affects accurate signal detection and robust generation of correct cell fates. Although many known regulatory mechanisms may reduce fluctuations in signals, most simultaneously influence their mean dynamics, leading to unfaithful cell fates. Through analysis and computation, w...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004218300348 |
| _version_ | 1819242510123270144 |
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| author | Christopher Rackauckas Thomas Schilling Qing Nie |
| author_facet | Christopher Rackauckas Thomas Schilling Qing Nie |
| author_sort | Christopher Rackauckas |
| collection | DOAJ |
| description | Summary: Stochasticity affects accurate signal detection and robust generation of correct cell fates. Although many known regulatory mechanisms may reduce fluctuations in signals, most simultaneously influence their mean dynamics, leading to unfaithful cell fates. Through analysis and computation, we demonstrate that a reversible signaling mechanism acting through intermediate states can reduce noise while maintaining the mean. This mean-independent noise control (MINC) mechanism is investigated in the context of an intracellular binding protein that regulates retinoic acid (RA) signaling during zebrafish hindbrain development. By comparing our models with experimental data, we find that the MINC mechanism allows for sharp boundaries of gene expression without sacrificing boundary accuracy. In addition, this MINC mechanism can modulate noise to levels that we show are beneficial to spatial patterning through noise-induced cell fate switching. These results reveal a design principle that may be important for noise regulation in many systems that control cell fate determination. : Developmental Biology; Bioinformatics; Systems Biology Subject Areas: Developmental Biology, Bioinformatics, Systems Biology |
| first_indexed | 2024-12-23T14:40:57Z |
| format | Article |
| id | doaj.art-26a9ef9114b24c92bead63cb80f0e433 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-23T14:40:57Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-26a9ef9114b24c92bead63cb80f0e4332022-12-21T17:43:12ZengElsevieriScience2589-00422018-05-0131120Mean-Independent Noise Control of Cell Fates via Intermediate StatesChristopher Rackauckas0Thomas Schilling1Qing Nie2Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USACenter for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USADepartment of Mathematics, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; Corresponding authorSummary: Stochasticity affects accurate signal detection and robust generation of correct cell fates. Although many known regulatory mechanisms may reduce fluctuations in signals, most simultaneously influence their mean dynamics, leading to unfaithful cell fates. Through analysis and computation, we demonstrate that a reversible signaling mechanism acting through intermediate states can reduce noise while maintaining the mean. This mean-independent noise control (MINC) mechanism is investigated in the context of an intracellular binding protein that regulates retinoic acid (RA) signaling during zebrafish hindbrain development. By comparing our models with experimental data, we find that the MINC mechanism allows for sharp boundaries of gene expression without sacrificing boundary accuracy. In addition, this MINC mechanism can modulate noise to levels that we show are beneficial to spatial patterning through noise-induced cell fate switching. These results reveal a design principle that may be important for noise regulation in many systems that control cell fate determination. : Developmental Biology; Bioinformatics; Systems Biology Subject Areas: Developmental Biology, Bioinformatics, Systems Biologyhttp://www.sciencedirect.com/science/article/pii/S2589004218300348 |
| spellingShingle | Christopher Rackauckas Thomas Schilling Qing Nie Mean-Independent Noise Control of Cell Fates via Intermediate States iScience |
| title | Mean-Independent Noise Control of Cell Fates via Intermediate States |
| title_full | Mean-Independent Noise Control of Cell Fates via Intermediate States |
| title_fullStr | Mean-Independent Noise Control of Cell Fates via Intermediate States |
| title_full_unstemmed | Mean-Independent Noise Control of Cell Fates via Intermediate States |
| title_short | Mean-Independent Noise Control of Cell Fates via Intermediate States |
| title_sort | mean independent noise control of cell fates via intermediate states |
| url | http://www.sciencedirect.com/science/article/pii/S2589004218300348 |
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