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Intrinsic and extrinsic noise of gene expression in lineage trees

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Title: Intrinsic and extrinsic noise of gene expression in lineage trees
Authors: Thomas, P
Item Type: Journal Article
Abstract: Cell-to-cell heterogeneity is driven by stochasticity in intracellular reactions and the population dynamics. While these sources are usually studied separately, we develop an agent-based framework that accounts for both factors while tracking every single cell of a growing population. Apart from the common intrinsic variability, the framework also predicts extrinsic noise without the need to introduce fluctuating rate constants. Instead, extrinsic fluctuations are explained by cell cycle fluctuations and differences in cell age. We provide explicit formulas to quantify mean molecule numbers, intrinsic and extrinsic noise statistics in two-colour experiments. We find that these statistics differ significantly depending on the experimental setup used to observe the cells. We illustrate this fact using (i) averages over an isolated cell lineage tracked over many generations as observed in the mother machine, (ii) population snapshots with known cell ages as recorded in time-lapse microscopy, and (iii) snapshots with unknown cell ages as measured from static images or flow cytometry. Applying the method to models of stochastic gene expression and feedback regulation elucidates that isolated lineages, as compared to snapshot data, can significantly overestimate the mean number of molecules, overestimate extrinsic noise but underestimate intrinsic noise and have qualitatively different sensitivities to cell cycle fluctuations.
Issue Date: 24-Jan-2019
Date of Acceptance: 8-Nov-2018
URI: http://hdl.handle.net/10044/1/66317
DOI: https://dx.doi.org/10.1038/s41598-018-35927-x
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 9
Issue: 1
Copyright Statement: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Royal Commission for the Exhibition of 1851
Open Access location: http://doi.org/10.1038/s41598-018-35927-x
Article Number: 474
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences



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