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Single-cell imaging and RNA sequencing reveal patterns of gene expression heterogeneity during fission yeast growth and adaptation

Saint, M; Bertaux, F; Tang, W; Sun, X-M; Game, L; Köferle, A; Bähler, J; ... Marguerat, S; + view all (2019) Single-cell imaging and RNA sequencing reveal patterns of gene expression heterogeneity during fission yeast growth and adaptation. Nature Microbiology , 4 (3) pp. 480-491. 10.1038/s41564-018-0330-4. Green open access

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Abstract

Phenotypic cell-to-cell variability is a fundamental determinant of microbial fitness that contributes to stress adaptation and drug resistance. Gene expression heterogeneity underpins this variability but is challenging to study genome-wide. Here we examine the transcriptomes of >2,000 single fission yeast cells exposed to various environmental conditions by combining imaging, single-cell RNA sequencing and Bayesian true count recovery. We identify sets of highly variable genes during rapid proliferation in constant culture conditions. By integrating single-cell RNA sequencing and cell-size data, we provide insights into genes that are regulated during cell growth and division, including genes whose expression does not scale with cell size. We further analyse the heterogeneity of gene expression during adaptive and acute responses to changing environments. Entry into the stationary phase is preceded by a gradual, synchronized adaptation in gene regulation that is followed by highly variable gene expression when growth decreases. Conversely, sudden and acute heat shock leads to a stronger, coordinated response and adaptation across cells. This analysis reveals that the magnitude of global gene expression heterogeneity is regulated in response to different physiological conditions within populations of a unicellular eukaryote.

Type: Article
Title: Single-cell imaging and RNA sequencing reveal patterns of gene expression heterogeneity during fission yeast growth and adaptation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41564-018-0330-4
Publisher version: https://doi.org/10.1038/s41564-018-0330-4
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: cellular microbiology, transcriptomics
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10068059
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