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

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Title: Single-cell imaging and RNA sequencing reveal patterns of gene expression heterogeneity during fission yeast growth and adaptation
Authors: Saint, M
Bertaux, F
Tang, W
Sun, X-M
Game, L
Köferle, A
Bähler, J
Shahrezaei, V
Marguerat, S
Item Type: Journal Article
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.
Issue Date: 4-Feb-2019
Date of Acceptance: 26-Nov-2018
URI: http://hdl.handle.net/10044/1/66903
DOI: https://dx.doi.org/10.1038/s41564-018-0330-4
ISSN: 2058-5276
Publisher: Nature Research
Start Page: 480
End Page: 491
Journal / Book Title: Nature Microbiology
Volume: 4
Copyright Statement: © The Author(s), under exclusive licence to Springer Nature Limited 2019
Publication Status: Published
Conference Place: England
Appears in Collections:Mathematics
Clinical Sciences
Molecular Sciences
Applied Mathematics and Mathematical Physics
Faculty of Medicine
Faculty of Natural Sciences



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