Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress
Abstract
From bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing to quantify transcript heterogeneity in single Saccharomyces cerevisiae cells treated with and without salt stress to explore population variation and identify cellular covariates that influence the stress-responsive transcriptome. Leveraging the extensive knowledge of yeast transcriptional regulation, we uncovered significant regulatory variation in individual yeast cells, both before and after stress. Moreover, we discovered that a subset of cells appears to decouple expression of ribosomal protein genes from the environmental stress response in a manner partly correlated with the cell cycle but unrelated to the yeast ultradian metabolic cycle. Live-cell imaging of cells expressing pairs of fluorescent regulators, including the transcription factor Msn2 with Dot6, Sfp1, or MAP kinase Hog1, revealed both coordinated and decoupled nucleocytoplasmic shuttling. Together with transcriptomic analysis, our results suggest that cells maintain a cellular filter against decoupled bursts of transcription factor activation but mount a stress response upon coordinated regulation, even in a subset of unstressed cells.
- Authors:
-
[1];
- Univ. of Wisconsin, Madison, WI (United States)
- Stanford Univ.,Stanford, CA (United States)
- Stanford Univ.,Stanford, CA (United States); Univ. of California San Diego, La Jolla, CA (United States)
- USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
- Stanford Univ.,Stanford, CA (United States); Chan Zuckerberg Biohub, San Francisco, CA, (United States)
- Hebrew Univ. of Jerusalem, Jerusalem (Israel)
- Publication Date:
- Research Org.:
- Univ. of Wisconsin, Madison, WI (United States); Univ. of California, Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1499873
- Grant/Contract Number:
- FC02-07ER64494; AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS biology (Online)
- Additional Journal Information:
- Journal Name: PLoS biology (Online); Journal Volume: 15; Journal Issue: 12; Journal ID: ISSN 1545-7885
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Gasch, Audrey P., Yu, Feiqiao Brian, Hose, James, Escalante, Leah E., Place, Mike, Bacher, Rhonda, Kanbar, Jad, Ciobanu, Doina, Sandor, Laura, Grigoriev, Igor V., Kendziorski, Christina, Quake, Stephen R., McClean, Megan N., and Balaban, Nathalie. Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress. United States: N. p., 2017.
Web. doi:10.1371/journal.pbio.2004050.
Gasch, Audrey P., Yu, Feiqiao Brian, Hose, James, Escalante, Leah E., Place, Mike, Bacher, Rhonda, Kanbar, Jad, Ciobanu, Doina, Sandor, Laura, Grigoriev, Igor V., Kendziorski, Christina, Quake, Stephen R., McClean, Megan N., & Balaban, Nathalie. Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress. United States. doi:10.1371/journal.pbio.2004050.
Gasch, Audrey P., Yu, Feiqiao Brian, Hose, James, Escalante, Leah E., Place, Mike, Bacher, Rhonda, Kanbar, Jad, Ciobanu, Doina, Sandor, Laura, Grigoriev, Igor V., Kendziorski, Christina, Quake, Stephen R., McClean, Megan N., and Balaban, Nathalie. Thu .
"Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress". United States. doi:10.1371/journal.pbio.2004050. https://www.osti.gov/servlets/purl/1499873.
@article{osti_1499873,
title = {Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress},
author = {Gasch, Audrey P. and Yu, Feiqiao Brian and Hose, James and Escalante, Leah E. and Place, Mike and Bacher, Rhonda and Kanbar, Jad and Ciobanu, Doina and Sandor, Laura and Grigoriev, Igor V. and Kendziorski, Christina and Quake, Stephen R. and McClean, Megan N. and Balaban, Nathalie},
abstractNote = {From bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing to quantify transcript heterogeneity in single Saccharomyces cerevisiae cells treated with and without salt stress to explore population variation and identify cellular covariates that influence the stress-responsive transcriptome. Leveraging the extensive knowledge of yeast transcriptional regulation, we uncovered significant regulatory variation in individual yeast cells, both before and after stress. Moreover, we discovered that a subset of cells appears to decouple expression of ribosomal protein genes from the environmental stress response in a manner partly correlated with the cell cycle but unrelated to the yeast ultradian metabolic cycle. Live-cell imaging of cells expressing pairs of fluorescent regulators, including the transcription factor Msn2 with Dot6, Sfp1, or MAP kinase Hog1, revealed both coordinated and decoupled nucleocytoplasmic shuttling. Together with transcriptomic analysis, our results suggest that cells maintain a cellular filter against decoupled bursts of transcription factor activation but mount a stress response upon coordinated regulation, even in a subset of unstressed cells.},
doi = {10.1371/journal.pbio.2004050},
journal = {PLoS biology (Online)},
number = 12,
volume = 15,
place = {United States},
year = {2017},
month = {12}
}
Search WorldCat to find libraries that may hold this journalWorks referenced in this record:
Bacterial Persistence as a Phenotypic Switch
journal, September 2004
- Balaban, Nathalie Q.; Merrin, Jack; Chait, Remy
- Science, Vol. 305, Issue 5690, p. 1622-1625