Patterns of interdivision time correlations reveal hidden cell cycle factors
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Published version
Author(s)
Hughes, Fern
Barr, Alexis
Thomas, Philipp
Type
Journal Article
Abstract
The time taken for cells to complete a round of cell division is a stochastic process controlled, in part, by intracellular factors. These factors can be inherited across cellular generations which gives rise to, often non-intuitive, correlation patterns in cell cycle timing between cells of different family relationships on lineage trees. Here, we formulate a framework of hidden inherited factors affecting the cell cycle that unifies known cell cycle control models and reveals three distinct interdivision time correlation patterns: aperiodic, alternator and oscillator. We use Bayesian inference with single-cell datasets of cell division in bacteria, mammalian and cancer cells, to identify the inheritance motifs that underlie these datasets. From our inference, we find that interdivision time correlation patterns do not identify a single cell cycle model but generally admit a broad posterior distribution of possible mechanisms. Despite this unidentifiability, we observe that the inferred patterns reveal interpretable inheritance dynamics and hidden rhythmicity of cell cycle factors. This reveals that cell cycle factors are commonly driven by circadian rhythms, but their period may differ in cancer. Our quantitative analysis thus reveals that correlation patterns are an emergent phenomenon that impact cell proliferation and these patterns may be altered in disease.
Date Issued
2023-01-06
Date Acceptance
2022-11-14
Citation
eLife, 2023, 11
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Journal / Book Title
eLife
Volume
11
Copyright Statement
© 2022, Hughes et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
License URL
Identifier
https://elifesciences.org/articles/80927
Publication Status
Published
Article Number
ARTN e80927
Date Publish Online
2022-11-15