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Non-genetic heterogeneity from stochastic partitioning at cell division

Nature Genetics volume 43, pages 95–100 (2011)Cite this article

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Abstract

Gene expression involves inherently probabilistic steps that create fluctuations in protein abundances. The results from many in-depth analyses and genome-scale surveys have suggested how such fluctuations arise and spread, often in ways consistent with stochastic models of transcription and translation. But fluctuations also arise during cell division when molecules are partitioned stochastically between the two daughters. Here we mathematically demonstrate how stochastic partitioning contributes to the non-genetic heterogeneity. Our results show that partitioning errors are hard to correct, and that the resulting noise profiles are remarkably difficult to separate from gene expression noise. By applying these results to common experimental strategies and distinguishing between creation versus transmission of noise, we hypothesize that much of the cell-to-cell heterogeneity that has been attributed to various aspects of gene expression instead comes from random segregation at cell division. We propose experiments to separate between these two types of fluctuations and discuss future directions.

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Figure 1: Growing and dividing cells.
Figure 2: Partitioning errors mimic gene expression noise.
Figure 3: Partitioning errors are difficult to effectively correct during the cell cycle.

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Acknowledgements

The research was supported by the National Science Foundation grants DMS-074876-0 and CAREER 0720056 and by grant GM081563-02 from the US National Institutes of Health. We thank I. Golding for valuable comments on the manuscript.

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Authors and Affiliations

  1. Department of Systems Biology, Harvard University, Boston, Massachusetts, USA

    Dann Huh & Johan Paulsson

  2. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA

    Dann Huh

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  1. Dann Huh
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Contributions

D.H. and J.P. jointly conceived the study, derived the results and wrote the paper.

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Correspondence to Johan Paulsson.

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The authors declare no competing financial interests.

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Huh, D., Paulsson, J. Non-genetic heterogeneity from stochastic partitioning at cell division. Nat Genet 43, 95–100 (2011). https://doi.org/10.1038/ng.729

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