Hidden long-range memories of growth and cycle speed correlate cell cycles in lineage trees
- German Cancer Research Center (DKFZ), Germany
Abstract
Cell heterogeneity may be caused by stochastic or deterministic effects. The inheritance of regulators through cell division is a key deterministic force, but identifying inheritance effects in a systematic manner has been challenging. Here we measure and analyze cell cycles in deep lineage trees of human cancer cells and mouse embryonic stem cells and develop a statistical framework to infer underlying rules of inheritance. The observed long-range intra-generational correlations in cell-cycle duration, up to second cousins, seem paradoxical because ancestral correlations decay rapidly. However, this correlation pattern is naturally explained by the inheritance of both cell size and cell-cycle speed over several generations, provided that cell growth and division are coupled through a minimum-size checkpoint. This model correctly predicts the effects of inhibiting cell growth or cycle progression. In sum, we show how fluctuations of cell cycles across lineage trees help understand the coordination of cell growth and division.
Data availability
Data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 and 4.
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RNA-Seq of SHEP TET21N cells upon Doxorubicin treatmentNCBI Gene Expression Omnibus, GSE98274.
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Author details
Funding
Bundesministerium für Bildung und Forschung (0316076A)
- Thomas Höfer
Bundesministerium für Bildung und Forschung (01ZX1307)
- Thomas Höfer
Bundesministerium für Bildung und Forschung (031L0087A)
- Thomas Höfer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Kuchen 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.
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Hidden long-range memories of growth and cycle speed correlate cell cycles in lineage trees
eLife 9:e51002.
https://doi.org/10.7554/eLife.51002
