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Single cell analysis of gene expression patterns during carbon starvation in Bacillus subtilis reveals large phenotypic variation

Authors

  • Imke G. de Jong,

    1. Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, AG, Groningen, The Netherlands
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  • Jan-Willem Veening,

    Corresponding author
    • Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, AG, Groningen, The Netherlands
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  • Oscar P. Kuipers

    Corresponding author
    1. Kluyver Center for Genomics of Industrial Fermentation, Groningen/Delft, Netherlands Genomics Initiative/Netherlands Organization for Scientific Research, The Netherlands
    • Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, AG, Groningen, The Netherlands
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For correspondence. E-mail j.w.veening@rug.nl; Tel. (+31) (0) 50 363 2408; Fax (+31) (0) 50 363 2348; E-mail o.p.kuipers@rug.nl; Tel. (+31) (0) 50 363 2093; Fax (+31) (0) 50 363 2348.

Summary

How cells dynamically respond to fluctuating environmental conditions depends on the architecture and noise of the underlying genetic circuits. Most work characterizing stress pathways in the model bacterium Bacillus subtilis has been performed on bulk cultures using ensemble assays. However, investigating the single cell response to stress is important since noise might generate significant phenotypic heterogeneity. Here, we study the stress response to carbon source starvation and compare both population and single cell data. Using a top-down approach, we investigate the transcriptional dynamics of various stress-related genes of B. subtilis in response to carbon source starvation and to increased cell density. Our data reveal that most of the tested gene-regulatory networks respond highly heterogeneously to starvation and cells show a large degree of variation in gene expression. The level of highly dynamic diversification within B. subtilis populations under changing environments reflects the necessity to study cells at the single cell level.

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