Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress

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

doi:10.1371/journal.pbio.2004050

Title: Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress

Journal Article · Thu Dec 14 00:00:00 EST 2017 · PLoS Biology (Online)

DOI:https://doi.org/10.1371/journal.pbio.2004050· OSTI ID:1499873

^[1]; Yu, Feiqiao Brian ^[2]; Hose, James ^[1]; Escalante, Leah E. ^[1]; Place, Mike ^[1]; Bacher, Rhonda ^[1]; Kanbar, Jad ^[3]; Ciobanu, Doina ^[4]; Sandor, Laura ^[4]; Grigoriev, Igor V. ^[4]; Kendziorski, Christina ^[1]; Quake, Stephen R. ^[5]; McClean, Megan N. ^[1]; Balaban, Nathalie ^[6]

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)

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. We also 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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Univ. of Wisconsin, Madison, WI (United States); University of California, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: FC02-07ER64494; AC02-05CH11231

OSTI ID:: 1499873

Alternate ID(s):: OSTI ID: 1619084

Journal Information:: PLoS Biology (Online), Vol. 15, Issue 12; ISSN 1545-7885

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 78 works

Citation information provided by
Web of Science

References (135)

Protein kinase A and TORC1 activate genes for ribosomal biogenesis by inactivating repressors encoded by Dot6 and its homolog Tod6 Lippman, S. I.; Broach, J. R. Proceedings of the National Academy of Sciences, Vol. 106, Issue 47 https://doi.org/10.1073/pnas.0907027106	journal	November 2009
Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses Petrenko, Natalia; Chereji, Raˇzvan V.; McClean, Megan N. Molecular Biology of the Cell, Vol. 24, Issue 12 https://doi.org/10.1091/mbc.e12-12-0870	journal	June 2013
Molecular mechanisms of ribosomal protein gene coregulation Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana Genes & Development, Vol. 29, Issue 18 https://doi.org/10.1101/gad.268896.115	journal	September 2015
Msn2 Coordinates a Stoichiometric Gene Expression Program Stewart-Ornstein, Jacob; Nelson, Christopher; DeRisi, Joe Current Biology, Vol. 23, Issue 23 https://doi.org/10.1016/j.cub.2013.09.043	journal	December 2013
SCnorm: robust normalization of single-cell RNA-seq data Bacher, Rhonda; Chu, Li-Fang; Leng, Ning Nature Methods, Vol. 14, Issue 6 https://doi.org/10.1038/nmeth.4263	journal	April 2017
Saccharomyces cerevisiae coordinates accumulation of yeast ribosomal proteins by modulating mRNA splicing, translational initiation, and protein turnover Warner, J. R.; Mitra, G.; Schwindinger, W. F. Molecular and Cellular Biology, Vol. 5, Issue 6 https://doi.org/10.1128/mcb.5.6.1512-1521.1985	journal	June 1985
p53 is a general repressor of RNA polymerase III transcription Cairns, C. A. The EMBO Journal, Vol. 17, Issue 11 https://doi.org/10.1093/emboj/17.11.3112	journal	June 1998
Comparative Analysis of Single-Cell RNA Sequencing Methods Ziegenhain, Christoph; Vieth, Beate; Parekh, Swati Molecular Cell, Vol. 65, Issue 4 https://doi.org/10.1016/j.molcel.2017.01.023	journal	February 2017
Single-Cell Analysis Reveals That Insulation Maintains Signaling Specificity Between Two Yeast MAPK Pathways with Common Components Patterson, J. C.; Klimenko, E. S.; Thorner, J. Science Signaling, Vol. 3, Issue 144 https://doi.org/10.1126/scisignal.2001275	journal	October 2010
Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise Newman, John R. S.; Ghaemmaghami, Sina; Ihmels, Jan Nature, Vol. 441, Issue 7095 https://doi.org/10.1038/nature04785	journal	May 2006
Bacterial Persistence as a Phenotypic Switch Balaban, Nathalie Q.; Merrin, Jack; Chait, Remy Science, Vol. 305, Issue 5690, p. 1622-1625 https://doi.org/10.1126/science.1099390	journal	September 2004
Ribosomal protein synthesis is not regulated at the translational level in Saccharomyces cerevisiae: balanced accumulation of ribosomal proteins L16 and rp59 is mediated by turnover of excess protein. Tsay, Y. F.; Thompson, J. R.; Rotenberg, M. O. Genes & Development, Vol. 2, Issue 6 https://doi.org/10.1101/gad.2.6.664	journal	June 1988
Growth control and ribosome biogenesis Lempiäinen, Harri; Shore, David Current Opinion in Cell Biology, Vol. 21, Issue 6 https://doi.org/10.1016/j.ceb.2009.09.002	journal	December 2009
Pathway connectivity and signaling coordination in the yeast stress‐activated signaling network Chasman, Deborah; Ho, Yi‐Hsuan; Berry, David B. Molecular Systems Biology, Vol. 10, Issue 11 https://doi.org/10.15252/msb.20145120	journal	November 2014
Bet Hedging in Yeast by Heterogeneous, Age-Correlated Expression of a Stress Protectant Levy, Sasha F.; Ziv, Naomi; Siegal, Mark L. PLoS Biology, Vol. 10, Issue 5 https://doi.org/10.1371/journal.pbio.1001325	journal	May 2012
Fast and accurate long-read alignment with Burrows–Wheeler transform Li, Heng; Durbin, Richard Bioinformatics, Vol. 26, Issue 5 https://doi.org/10.1093/bioinformatics/btp698	journal	January 2010
Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling Ho, Yi-Hsuan; Gasch, Audrey P. Current Genetics, Vol. 61, Issue 4 https://doi.org/10.1007/s00294-015-0491-0	journal	May 2015
The importance of being persistent: heterogeneity of bacterial populations under antibiotic stress Gefen, Orit; Balaban, Nathalie Q. FEMS Microbiology Reviews, Vol. 33, Issue 4 https://doi.org/10.1111/j.1574-6976.2008.00156.x	journal	July 2009
The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress Alejandro-Osorio, Adriana L.; Huebert, Dana J.; Porcaro, Dominic T. Genome Biology, Vol. 10, Issue 5 https://doi.org/10.1186/gb-2009-10-5-r57	journal	January 2009
Balanced Production of Ribosome Components Is Required for Proper G ₁ /S Transition in Saccharomyces cerevisiae Gómez-Herreros, Fernando; Rodríguez-Galán, Olga; Morillo-Huesca, Macarena Journal of Biological Chemistry, Vol. 288, Issue 44 https://doi.org/10.1074/jbc.M113.500488	journal	September 2013
Characterizing transcriptional heterogeneity through pathway and gene set overdispersion analysis Fan, Jean; Salathia, Neeraj; Liu, Rui Nature Methods, Vol. 13, Issue 3 https://doi.org/10.1038/nmeth.3734	journal	January 2016
Multiple Means to the Same End: The Genetic Basis of Acquired Stress Resistance in Yeast Berry, David B.; Guan, Qiaoning; Hose, James PLoS Genetics, Vol. 7, Issue 11 https://doi.org/10.1371/journal.pgen.1002353	journal	November 2011
Remodeling of Yeast Genome Expression in Response to Environmental Changes Causton, Helen C.; Ren, Bing; Koh, Sang Seok Molecular Biology of the Cell, Vol. 12, Issue 2 https://doi.org/10.1091/mbc.12.2.323	journal	February 2001
Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A.; Ilicic, Tomislav Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms9687	journal	October 2015
Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism and Cell Cycle in S. cerevisiae Zhao, Gang; Chen, Yuping; Carey, Lucas Molecular Cell, Vol. 62, Issue 4 https://doi.org/10.1016/j.molcel.2016.04.026	journal	May 2016
Classification of low quality cells from single-cell RNA-seq data. Ilicic, Tomislav; Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.40034	text	January 2016
Cellular Heterogeneity: Benefits Besides Bet-Hedging Levy, Sasha F. Current Biology, Vol. 26, Issue 9 https://doi.org/10.1016/j.cub.2016.03.034	journal	May 2016
Hog1 Targets Whi5 and Msa1 Transcription Factors To Downregulate Cyclin Expression upon Stress González-Novo, Alberto; Jiménez, Javier; Clotet, Josep Molecular and Cellular Biology, Vol. 35, Issue 9 https://doi.org/10.1128/MCB.01279-14	journal	March 2015
Cluster analysis and display of genome-wide expression patterns Eisen, M. B.; Spellman, P. T.; Brown, P. O. Proceedings of the National Academy of Sciences, Vol. 95, Issue 25 https://doi.org/10.1073/pnas.95.25.14863	journal	December 1998
Metabolic cycling in single yeast cells from unsynchronized steady-state populations limited on glucose or phosphate Silverman, S. J.; Petti, A. A.; Slavov, N. Proceedings of the National Academy of Sciences, Vol. 107, Issue 15 https://doi.org/10.1073/pnas.1002422107	journal	March 2010
Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L Huber, Alexandre; French, Sarah L.; Tekotte, Hille The EMBO Journal, Vol. 30, Issue 15 https://doi.org/10.1038/emboj.2011.221	journal	July 2011
Imaging individual mRNA molecules using multiple singly labeled probes Raj, Arjun; van den Bogaard, Patrick; Rifkin, Scott A. Nature Methods, Vol. 5, Issue 10 https://doi.org/10.1038/nmeth.1253	journal	September 2008
Regulated cell-to-cell variation in a cell-fate decision system Colman-Lerner, Alejandro; Gordon, Andrew; Serra, Eduard Nature, Vol. 437, Issue 7059 https://doi.org/10.1038/nature03998	journal	September 2005
Promoter decoding of transcription factor dynamics involves a trade‐off between noise and control of gene expression Hansen, Anders S.; O'Shea, Erin K. Molecular Systems Biology, Vol. 9, Issue 1 https://doi.org/10.1038/msb.2013.56	journal	January 2013
Schedule-dependent interaction between anticancer treatments Chen, Sheng-hong; Forrester, William; Lahav, Galit Science, Vol. 351, Issue 6278 https://doi.org/10.1126/science.aac5610	journal	March 2016
Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression. Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A.; Ilicic, Tomislav Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.40042	text	January 2015
Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1 Escoté, Xavier; Zapater, Meritxell; Clotet, Josep Nature Cell Biology, Vol. 6, Issue 10 https://doi.org/10.1038/ncb1174	journal	September 2004
Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation P., Ward, Mary; Angela, Smith,; Stephen, Garrett, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/swtm-0n76	text	January 1998
Exploiting Natural Variation in Saccharomyces cerevisiae to Identify Genes for Increased Ethanol Resistance Lewis, Jeffrey A.; Elkon, Isaac M.; McGee, Mick A. Genetics, Vol. 186, Issue 4 https://doi.org/10.1534/genetics.110.121871	journal	September 2010
Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq experiments Leng, Ning; Chu, Li-Fang; Barry, Chris Nature Methods, Vol. 12, Issue 10 https://doi.org/10.1038/nmeth.3549	journal	August 2015
cis Determinants of Promoter Threshold and Activation Timescale Hansen, Anders S.; O’Shea, Erin K. Cell Reports, Vol. 12, Issue 8 https://doi.org/10.1016/j.celrep.2015.07.035	journal	August 2015
Pulsatile Dynamics in the Yeast Proteome Dalal, Chiraj K.; Cai, Long; Lin, Yihan Current Biology, Vol. 24, Issue 18 https://doi.org/10.1016/j.cub.2014.07.076	journal	September 2014
Encoding four gene expression programs in the activation dynamics of a single transcription factor Hansen, Anders S.; O’Shea, Erin K. Current Biology, Vol. 26, Issue 7 https://doi.org/10.1016/j.cub.2016.02.058	journal	April 2016
A dynamic model of proteome changes reveals new roles for transcript alteration in yeast Lee, M. Violet; Topper, Scott E.; Hubler, Shane L. Molecular Systems Biology, Vol. 7, Issue 1 https://doi.org/10.1038/msb.2011.48	journal	January 2011
Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes Chymkowitch, P.; Eldholm, V.; Lorenz, S. Proceedings of the National Academy of Sciences, Vol. 109, Issue 26 https://doi.org/10.1073/pnas.1200067109	journal	June 2012
Transcriptional Regulation by P53 Beckerman, R.; Prives, C. Cold Spring Harbor Perspectives in Biology, Vol. 2, Issue 8 https://doi.org/10.1101/cshperspect.a000935	journal	April 2010
Don't let sleeping cells lie Villanueva, Teresa Nature Reviews Cancer, Vol. 10, Issue 7 https://doi.org/10.1038/nrc2884	journal	June 2010
Batch effects and the effective design of single-cell gene expression studies Tung, Po-Yuan; Blischak, John D.; Hsiao, Chiaowen Joyce Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/srep39921	journal	January 2017
Cellular Noise Regulons Underlie Fluctuations in Saccharomyces cerevisiae Stewart-Ornstein, Jacob; Weissman, Jonathan S.; El-Samad, Hana Molecular Cell, Vol. 45, Issue 4 https://doi.org/10.1016/j.molcel.2011.11.035	journal	February 2012
Cell cycle population effects in perturbation studies O'Duibhir, Eoghan; Lijnzaad, Philip; Benschop, Joris J. Molecular Systems Biology, Vol. 10, Issue 6 https://doi.org/10.15252/msb.20145172	journal	June 2014
Drugging Drug Resistance Dannenberg, Jan-Hermen; Berns, Anton Cell, Vol. 141, Issue 1 https://doi.org/10.1016/j.cell.2010.03.020	journal	April 2010
Growth control of the eukaryote cell: a systems biology study in yeast Castrillo, Juan I.; Zeef, Leo A.; Hoyle, David C. Journal of Biology, Vol. 6, Issue 2 https://doi.org/10.1186/jbiol54	journal	January 2007
The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors Beck, Thomas; Hall, Michael N. Nature, Vol. 402, Issue 6762 https://doi.org/10.1038/45287	journal	December 1999
Control of Stochasticity in Eukaryotic Gene Expression Raser, J. M. Science, Vol. 304, Issue 5678 https://doi.org/10.1126/science.1098641	journal	June 2004
Slow Growth Induces Heat-Shock Resistance in Normal and Respiratory-deficient Yeast Lu, Charles; Brauer, Matthew J.; Botstein, David Molecular Biology of the Cell, Vol. 20, Issue 3 https://doi.org/10.1091/mbc.e08-08-0852	journal	February 2009
Epigenetics make transient states of cancer therapy resistance permanent Sarosiek, Kristopher Science Translational Medicine, Vol. 9, Issue 396 https://doi.org/10.1126/scitranslmed.aan6729	journal	June 2017
A Systems-Level Analysis of Perfect Adaptation in Yeast Osmoregulation Muzzey, Dale; Gómez-Uribe, Carlos A.; Mettetal, Jerome T. Journal of End-to-End-testing, Vol. 138, Issue 1 https://doi.org/10.1016/s9999-9994(09)20366-7	journal	July 2009
Phenotypic Consequences of Promoter-Mediated Transcriptional Noise Blake, William J.; Balázsi, Gábor; Kohanski, Michael A. Molecular Cell, Vol. 24, Issue 6 https://doi.org/10.1016/j.molcel.2006.11.003	journal	December 2006
Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation Smith, A. The EMBO Journal, Vol. 17, Issue 13 https://doi.org/10.1093/emboj/17.13.3556	journal	July 1998
Ribosomal protein L32 of Saccharomyces cerevisiae influences both the splicing of its own transcript and the processing of rRNA. Vilardell, J.; Warner, J. R. Molecular and Cellular Biology, Vol. 17, Issue 4 https://doi.org/10.1128/MCB.17.4.1959	journal	April 1997
Persistence to anti-cancer treatments in the stationary to proliferating transition Pearl Mizrahi, Sivan; Gefen, Orit; Simon, Itamar Cell Cycle, Vol. 15, Issue 24 https://doi.org/10.1080/15384101.2016.1248006	journal	October 2016
Noise in protein expression scales with natural protein abundance Bar-Even, Arren; Paulsson, Johan; Maheshri, Narendra Nature Genetics, Vol. 38, Issue 6 https://doi.org/10.1038/ng1807	journal	May 2006
Combinatorial gene regulation by modulation of relative pulse timing Lin, Yihan; Sohn, Chang Ho; Dalal, Chiraj K. Nature, Vol. 527, Issue 7576 https://doi.org/10.1038/nature15710	journal	October 2015
Logic of the Yeast Metabolic Cycle: Temporal Compartmentalization of Cellular Processes Tu, B. P. Science, Vol. 310, Issue 5751 https://doi.org/10.1126/science.1120499	journal	November 2005
A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations Sharma, Sreenath V.; Lee, Diana Y.; Li, Bihua Cell, Vol. 141, Issue 1 https://doi.org/10.1016/j.cell.2010.02.027	journal	April 2010
Bayesian approach to single-cell differential expression analysis Kharchenko, Peter V.; Silberstein, Lev; Scadden, David T. Nature Methods, Vol. 11, Issue 7 https://doi.org/10.1038/nmeth.2967	journal	May 2014
Frequency-modulated nuclear localization bursts coordinate gene regulation Cai, Long; Dalal, Chiraj K.; Elowitz, Michael B. Nature, Vol. 455, Issue 7212 https://doi.org/10.1038/nature07292	journal	September 2008
From single-cell to cell-pool transcriptomes: Stochasticity in gene expression and RNA splicing Marinov, G. K.; Williams, B. A.; McCue, K. Genome Research, Vol. 24, Issue 3 https://doi.org/10.1101/gr.161034.113	journal	December 2013
p53 represses ribosomal gene transcription Budde, Andreja; Grummt, Ingrid Oncogene, Vol. 18, Issue 4 https://doi.org/10.1038/sj.onc.1202402	journal	January 1999
High-resolution DNA-binding specificity analysis of yeast transcription factors Zhu, C.; Byers, K. J. R. P.; McCord, R. P. Genome Research, Vol. 19, Issue 4 https://doi.org/10.1101/gr.090233.108	journal	January 2009
Phagocytosis-like cell engulfment by a planctomycete bacterium Shiratori, Takashi; Suzuki, Shigekatsu; Kakizawa, Yukako Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13499-2	journal	December 2019
Genomic Expression Responses to DNA-damaging Agents and the Regulatory Role of the Yeast ATR Homolog Mec1p Gasch, Audrey P.; Huang, Mingxia; Metzner, Sandra Molecular Biology of the Cell, Vol. 12, Issue 10 https://doi.org/10.1091/mbc.12.10.2987	journal	October 2001
Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression Marion, R. M.; Regev, A.; Segal, E. Proceedings of the National Academy of Sciences, Vol. 101, Issue 40 https://doi.org/10.1073/pnas.0405353101	journal	September 2004
Cell cycle Start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates Burnetti, Anthony J.; Aydin, Mert; Buchler, Nicolas E. Molecular Biology of the Cell, Vol. 27, Issue 1 https://doi.org/10.1091/mbc.e15-07-0454	journal	January 2016
Coupling among growth rate response, metabolic cycle, and cell division cycle in yeast Slavov, Nikolai; Botstein, David Molecular Biology of the Cell, Vol. 22, Issue 12 https://doi.org/10.1091/mbc.e11-02-0132	journal	June 2011
When Noisy Neighbors Are a Blessing: Analysis of Gene Expression Noise Identifies Coregulated Genes Junker, Jan Philipp; van Oudenaarden, Alexander Molecular Cell, Vol. 45, Issue 4 https://doi.org/10.1016/j.molcel.2012.02.002	journal	February 2012
Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity Klein, C.; Struhl, K. Molecular and Cellular Biology, Vol. 14, Issue 3 https://doi.org/10.1128/mcb.14.3.1920-1928.1994	journal	March 1994
Characterization of the p53 Cistrome – DNA Binding Cooperativity Dissects p53's Tumor Suppressor Functions Schlereth, Katharina; Heyl, Charlotte; Krampitz, Anna-Maria PLoS Genetics, Vol. 9, Issue 8 https://doi.org/10.1371/journal.pgen.1003726	journal	August 2013
Production of viable chicken by allogeneic transplantation of primordial germ cells induced from somatic cells Zhao, Ruifeng; Zuo, Qisheng; Yuan, Xia Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-23242-5	journal	May 2021
Fiji: an open-source platform for biological-image analysis Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin Nature Methods, Vol. 9, Issue 7 https://doi.org/10.1038/nmeth.2019	journal	June 2012
CellProfiler and KNIME: Open Source Tools for High Content Screening Stöter, Martin; Niederlein, Antje; Barsacchi, Rico Target Identification and Validation in Drug Discovery https://doi.org/10.1007/978-1-62703-311-4_8	book	January 2013
Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor Gorner, W. The EMBO Journal, Vol. 21, Issue 1 https://doi.org/10.1093/emboj/21.1.135	journal	January 2002
p53 Dynamics Control Cell Fate Purvis, J. E.; Karhohs, K. W.; Mock, C. Science, Vol. 336, Issue 6087 https://doi.org/10.1126/science.1218351	journal	June 2012
Contributions of low molecule number and chromosomal positioning to stochastic gene expression Becskei, Attila; Kaufmann, Benjamin B.; van Oudenaarden, Alexander Nature Genetics, Vol. 37, Issue 9 https://doi.org/10.1038/ng1616	journal	August 2005
Quantification of the yeast transcriptome by single-molecule sequencing Lipson, Doron; Raz, Tal; Kieu, Alix Nature Biotechnology, Vol. 27, Issue 7 https://doi.org/10.1038/nbt.1551	journal	July 2009
YEASTRACT: providing a programmatic access to curated transcriptional regulatory associations in Saccharomyces cerevisiae through a web services interface Abdulrehman, D.; Monteiro, P. T.; Teixeira, M. C. Nucleic Acids Research, Vol. 39, Issue Database https://doi.org/10.1093/nar/gkq964	journal	October 2010
Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance Shaffer, Sydney M.; Dunagin, Margaret C.; Torborg, Stefan R. Nature, Vol. 546, Issue 7658 https://doi.org/10.1038/nature22794	journal	June 2017
Global analysis of protein expression in yeast Ghaemmaghami, Sina; Huh, Won-Ki; Bower, Kiowa Nature, Vol. 425, Issue 6959 https://doi.org/10.1038/nature02046	journal	October 2003
Slow-Cycling Therapy-Resistant Cancer Cells Moore, Nathan; Houghton, JeanMarie; Lyle, Stephen Stem Cells and Development, Vol. 21, Issue 10 https://doi.org/10.1089/scd.2011.0477	journal	July 2012
Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation López-Maury, Luis; Marguerat, Samuel; Bähler, Jürg Nature Reviews Genetics, Vol. 9, Issue 8 https://doi.org/10.1038/nrg2398	journal	August 2008
Methods of Digital Video Microscopy for Colloidal Studies Crocker, John C.; Grier, David G. Journal of Colloid and Interface Science, Vol. 179, Issue 1 https://doi.org/10.1006/jcis.1996.0217	journal	April 1996
Tunable Signal Processing Through Modular Control of Transcription Factor Translocation Hao, N.; Budnik, B. A.; Gunawardena, J. Science, Vol. 339, Issue 6118 https://doi.org/10.1126/science.1227299	journal	January 2013
Commitment to a Cellular Transition Precedes Genome-wide Transcriptional Change Eser, Umut; Falleur-Fettig, Melody; Johnson, Amy Molecular Cell, Vol. 43, Issue 4 https://doi.org/10.1016/j.molcel.2011.06.024	journal	August 2011
Noise in Gene Expression: Origins, Consequences, and Control Raser, J. M. Science, Vol. 309, Issue 5743 https://doi.org/10.1126/science.1105891	journal	September 2005
Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1 Ferrigno, P. The EMBO Journal, Vol. 17, Issue 19 https://doi.org/10.1093/emboj/17.19.5606	journal	October 1998
The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression Ewald, Jennifer C.; Kuehne, Andreas; Zamboni, Nicola Molecular Cell, Vol. 62, Issue 4 https://doi.org/10.1016/j.molcel.2016.02.017	journal	May 2016
Nucleocytoplasmic Oscillations of the Yeast Transcription Factor Msn2: Evidence for Periodic PKA Activation Garmendia-Torres, Cecilia; Goldbeter, Albert; Jacquet, Michel Current Biology, Vol. 17, Issue 12 https://doi.org/10.1016/j.cub.2007.05.032	journal	June 2007
Persistence to anti-cancer treatments in the stationary to proliferating transition Mizrahi, Sivan Pearl; Gefen, Orit; Simon, Itamar Taylor & Francis https://doi.org/10.6084/m9.figshare.4165659	dataset	January 2016
Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators Msn2 and Msn4 in Saccharomyces cerevisiae Jacquet, Michel; Renault, Georges; Lallet, Sylvie The Journal of Cell Biology, Vol. 161, Issue 3 https://doi.org/10.1083/jcb.200303030	journal	May 2003
Up-to-date catalogues of yeast protein complexes Pu, Shuye; Wong, Jessica; Turner, Brian Nucleic Acids Research, Vol. 37, Issue 3 https://doi.org/10.1093/nar/gkn1005	journal	December 2008
Chromatin decouples promoter threshold from dynamic range Lam, Felix H.; Steger, David J.; O’Shea, Erin K. Nature, Vol. 453, Issue 7192 https://doi.org/10.1038/nature06867	journal	April 2008
Identification and Distinct Regulation of Yeast TATA Box-Containing Genes Basehoar, Andrew D.; Zanton, Sara J.; Pugh, B. Franklin Cell, Vol. 116, Issue 5 https://doi.org/10.1016/s0092-8674(04)00205-3	journal	March 2004
The role of physiological heterogeneity in microbial population behavior Lidstrom, Mary E.; Konopka, Michael C. Nature Chemical Biology, Vol. 6, Issue 10 https://doi.org/10.1038/nchembio.436	journal	September 2010
Signal-dependent dynamics of transcription factor translocation controls gene expression Hao, Nan; O'Shea, Erin K. Nature Structural & Molecular Biology, Vol. 19, Issue 1 https://doi.org/10.1038/nsmb.2192	journal	December 2011
Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization Spellman, Paul T.; Sherlock, Gavin; Zhang, Michael Q. Molecular Biology of the Cell, Vol. 9, Issue 12 https://doi.org/10.1091/mbc.9.12.3273	journal	December 1998
Sfp1 Plays a Key Role in Yeast Ribosome Biogenesis Fingerman, Ian; Nagaraj, Vijayalakshmi; Norris, David Eukaryotic Cell, Vol. 2, Issue 5 https://doi.org/10.1128/EC.2.5.1061-1068.2003	journal	October 2003
Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity Gorner, W.; Durchschlag, E.; Martinez-Pastor, M. T. Genes & Development, Vol. 12, Issue 4 https://doi.org/10.1101/gad.12.4.586	journal	February 1998
Dynamic Changes in Nucleosome Occupancy Are Not Predictive of Gene Expression Dynamics but Are Linked to Transcription and Chromatin Regulators Huebert, D. J.; Kuan, P. -F.; Keles, S. Molecular and Cellular Biology, Vol. 32, Issue 9 https://doi.org/10.1128/MCB.06170-11	journal	February 2012
Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage van Dijk, David; Dhar, Riddhiman; Missarova, Alsu M. Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms8972	journal	August 2015
Classification of low quality cells from single-cell RNA-seq data Ilicic, Tomislav; Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A. Genome Biology, Vol. 17, Issue 1 https://doi.org/10.1186/s13059-016-0888-1	journal	February 2016
Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm Chu, Li-Fang; Leng, Ning; Zhang, Jue Genome Biology, Vol. 17, Issue 1 https://doi.org/10.1186/s13059-016-1033-x	journal	August 2016
Single-RNA counting reveals alternative modes of gene expression in yeast Zenklusen, Daniel; Larson, Daniel R.; Singer, Robert H. Nature Structural & Molecular Biology, Vol. 15, Issue 12 https://doi.org/10.1038/nsmb.1514	journal	November 2008
Affinity and competition for TBP are molecular determinants of gene expression noise Ravarani, Charles N. J.; Chalancon, Guilhem; Breker, Michal Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms10417	journal	February 2016
Transcriptional regulatory code of a eukaryotic genome Harbison, Christopher T.; Gordon, D. Benjamin; Lee, Tong Ihn Nature, Vol. 431, Issue 7004 https://doi.org/10.1038/nature02800	journal	September 2004
A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor Growth Roesch, Alexander; Fukunaga-Kalabis, Mizuho; Schmidt, Elizabeth C. Cell, Vol. 141, Issue 4 https://doi.org/10.1016/j.cell.2010.04.020	journal	May 2010
Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity. Klein, C.; Struhl, K. Molecular and Cellular Biology, Vol. 14, Issue 3 https://doi.org/10.1128/MCB.14.3.1920	journal	March 1994
Poised epigenetic states and acquired drug resistance in cancer Brown, Robert; Curry, Edward; Magnani, Luca Nature Reviews Cancer, Vol. 14, Issue 11 https://doi.org/10.1038/nrc3819	journal	September 2014
Noise and Epigenetic Inheritance of Single-Cell Division Times Influence Population Fitness Cerulus, Bram; New, Aaron M.; Pougach, Ksenia Current Biology, Vol. 26, Issue 9 https://doi.org/10.1016/j.cub.2016.03.010	journal	May 2016
A non-invasive method to generate induced pluripotent stem cells from primate urine Geuder, Johanna; Wange, Lucas E.; Janjic, Aleksandar Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-82883-0	journal	February 2021
Autonomous Metabolic Oscillations Robustly Gate the Early and Late Cell Cycle Papagiannakis, Alexandros; Niebel, Bastian; Wit, Ernst C. Molecular Cell, Vol. 65, Issue 2 https://doi.org/10.1016/j.molcel.2016.11.018	journal	January 2017
Saccharomyces cerevisiae coordinates accumulation of yeast ribosomal proteins by modulating mRNA splicing, translational initiation, and protein turnover. Warner, J. R.; Mitra, G.; Schwindinger, W. F. Molecular and Cellular Biology, Vol. 5, Issue 6 https://doi.org/10.1128/MCB.5.6.1512	journal	June 1985
Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes Gasch, Audrey P.; Spellman, Paul T.; Kao, Camilla M. Molecular Biology of the Cell, Vol. 11, Issue 12 https://doi.org/10.1091/mbc.11.12.4241	journal	December 2000
Homeostatic Adjustment and Metabolic Remodeling in Glucose-limited Yeast Cultures Brauer, Matthew J.; Saldanha, Alok J.; Dolinski, Kara Molecular Biology of the Cell, Vol. 16, Issue 5 https://doi.org/10.1091/mbc.E04-11-0968	journal	May 2005
A Comprehensive Genomic Binding Map of Gene and Chromatin Regulatory Proteins in Saccharomyces Venters, Bryan J.; Wachi, Shinichiro; Mavrich, Travis N. Molecular Cell, Vol. 41, Issue 4 https://doi.org/10.1016/j.molcel.2011.01.015	journal	February 2011
Stress-activated Genomic Expression Changes Serve a Preparative Role for Impending Stress in Yeast Berry, David B.; Gasch, Audrey P. Molecular Biology of the Cell, Vol. 19, Issue 11 https://doi.org/10.1091/mbc.e07-07-0680	journal	November 2008
Keeping p53 in Check: A High-Stakes Balancing Act Berger, Shelley L. Cell, Vol. 142, Issue 1 https://doi.org/10.1016/j.cell.2010.06.026	journal	July 2010
Dynamic control of gene regulatory logic by seemingly redundant transcription factors AkhavanAghdam, Zohreh; Sinha, Joydeb; Tabbaa, Omar P. eLife, Vol. 5 https://doi.org/10.7554/eLife.18458	journal	September 2016
A Systems-Level Analysis of Perfect Adaptation in Yeast Osmoregulation Muzzey, Dale; Gómez-Uribe, Carlos A.; Mettetal, Jerome T. Cell, Vol. 138, Issue 1 https://doi.org/10.1016/j.cell.2009.04.047	journal	July 2009
Ribosome Biogenesis Is Sensed at the Start Cell Cycle Checkpoint Bernstein, Kara A.; Bleichert, Franziska; Bean, James M. Molecular Biology of the Cell, Vol. 18, Issue 3 https://doi.org/10.1091/mbc.e06-06-0512	journal	March 2007
Saccharomyces Genome Database: the genomics resource of budding yeast Cherry, J. M.; Hong, E. L.; Amundsen, C. Nucleic Acids Research, Vol. 40, Issue D1 https://doi.org/10.1093/nar/gkr1029	journal	November 2011
TOR Regulates Ribosomal Protein Gene Expression via PKA and the Forkhead Transcription Factor FHL1 Martin, Dietmar E.; Soulard, Alexandre; Hall, Michael N. Cell, Vol. 119, Issue 7 https://doi.org/10.1016/j.cell.2004.11.047	journal	December 2004
Basal Dynamics of p53 Reveal Transcriptionally Attenuated Pulses in Cycling Cells Loewer, Alexander; Batchelor, Eric; Gaglia, Giorgio Cell, Vol. 142, Issue 1 https://doi.org/10.1016/j.cell.2010.05.031	journal	July 2010
Proteasomal degradation of Sfp1 contributes to the repression of ribosome biogenesis during starvation and is mediated by the proteasome activator Blm10 Lopez, Antonio Diaz; Tar, Krisztina; Krügel, Undine Molecular Biology of the Cell, Vol. 22, Issue 5 https://doi.org/10.1091/mbc.e10-04-0352	journal	March 2011
Persistence to Anti-Cancer Treatments in the Stationary to Proliferating Transition Mizrahi, Sivan Pearl; Gefen, Orit; Simon, Itamar Taylor & Francis https://doi.org/10.6084/m9.figshare.4165659.v1	dataset	January 2016
The yeast ribosomal protein L32 and its gene. Dabeva, M. D.; Warner, J. R. Journal of Biological Chemistry, Vol. 262, Issue 33 https://doi.org/10.1016/S0021-9258(18)47695-8	journal	November 1987

Cited By (23)

The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs Marchant, Axelle; Cisneros, Angel F.; Dubé, Alexandre K. eLife, Vol. 8 https://doi.org/10.7554/elife.46754	journal	August 2019
Control of nongenetic heterogeneity in growth rate and stress tolerance of Saccharomyces cerevisiae by cyclic AMP-regulated transcription factors Li, Shuang; Giardina, Daniella M.; Siegal, Mark L. PLOS Genetics, Vol. 14, Issue 11 https://doi.org/10.1371/journal.pgen.1007744	journal	November 2018
Widespread inter‐individual gene expression variability in Arabidopsis thaliana Cortijo, Sandra; Aydin, Zeynep; Ahnert, Sebastian Molecular Systems Biology, Vol. 15, Issue 1 https://doi.org/10.15252/msb.20188591	journal	January 2019
Systematic genetics and single‐cell imaging reveal widespread morphological pleiotropy and cell‐to‐cell variability Mattiazzi Usaj, Mojca; Sahin, Nil; Friesen, Helena Molecular Systems Biology, Vol. 16, Issue 2 https://doi.org/10.15252/msb.20199243	journal	February 2020
Sensitive high-throughput single-cell RNA-seq reveals within-clonal transcript correlations in yeast populations Nadal-Ribelles, Mariona; Islam, Saiful; Wei, Wu Nature Microbiology, Vol. 4, Issue 4 https://doi.org/10.1038/s41564-018-0346-9	journal	February 2019
The renaissance of yeasts as microbial factories in the modern age of biomanufacturing Payen, Celia; Thompson, Dawn Yeast, Vol. 36, Issue 12 https://doi.org/10.1002/yea.3439	journal	September 2019
Distributed and dynamic intracellular organization of extracellular information Granados, Alejandro A.; Pietsch, Julian M. J.; Cepeda-Humerez, Sarah A. Proceedings of the National Academy of Sciences, Vol. 115, Issue 23 https://doi.org/10.1073/pnas.1716659115	journal	May 2018
Exactly solvable models of stochastic gene expression Ham, Lucy; Schnoerr, David; Brackston, Rowan D. The Journal of Chemical Physics, Vol. 152, Issue 14 https://doi.org/10.1063/1.5143540	journal	April 2020
Complex genetic and epigenetic regulation deviates gene expression from a unifying global transcriptional program Chagoyen, Mónica; Poyatos, Juan F. PLOS Computational Biology, Vol. 15, Issue 9 https://doi.org/10.1371/journal.pcbi.1007353	journal	September 2019
The genetic basis of aneuploidy tolerance in wild yeast Hose, James; Escalante, Leah E.; Clowers, Katie J. eLife, Vol. 9 https://doi.org/10.7554/elife.52063	journal	January 2020
High throughput gene expression profiling of yeast colonies with microgel-culture Drop-seq Liu, Leqian; Dalal, Chiraj K.; Heineike, Benjamin M. Lab on a Chip, Vol. 19, Issue 10 https://doi.org/10.1039/c9lc00084d	journal	January 2019
Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging Walzer, Katelyn A.; Fradin, Hélène; Emerson, Liane Y. PLOS Genetics, Vol. 15, Issue 12 https://doi.org/10.1371/journal.pgen.1008506	journal	December 2019
Single-Cell RNA Sequencing-Based Computational Analysis to Describe Disease Heterogeneity Zeng, Tao; Dai, Hao Frontiers in Genetics, Vol. 10 https://doi.org/10.3389/fgene.2019.00629	journal	July 2019
Single-cell RNA sequencing reveals a heterogeneous response to Glucocorticoids in breast cancer cells Hoffman, Jackson A.; Papas, Brian N.; Trotter, Kevin W. Communications Biology, Vol. 3, Issue 1 https://doi.org/10.1038/s42003-020-0837-0	journal	March 2020
Single-cell imaging and RNA sequencing reveal patterns of gene expression heterogeneity during fission yeast growth and adaptation Saint, Malika; Bertaux, François; Tang, Wenhao Nature Microbiology, Vol. 4, Issue 3 https://doi.org/10.1038/s41564-018-0330-4	journal	February 2019
A consensus S. cerevisiae metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism Lu, Hongzhong; Li, Feiran; Sánchez, Benjamín J. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-11581-3	journal	August 2019
Time-lapse single-cell transcriptomics reveals modulation of histone H3 for dormancy breaking in fission yeast Tsuyuzaki, Hayato; Hosokawa, Masahito; Arikawa, Koji Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-15060-y	journal	March 2020
Transcriptome visualization and data availability at the Saccharomyces Genome Database Ng, Patrick C.; Wong, Edith D.; MacPherson, Kevin A. Nucleic Acids Research, Vol. 48, Issue D1 https://doi.org/10.1093/nar/gkz892	journal	October 2019
Single-Cell RNA Sequencing of Plant-Associated Bacterial Communities Ma, Qin; Bücking, Heike; Gonzalez Hernandez, Jose L. Frontiers in Microbiology, Vol. 10 https://doi.org/10.3389/fmicb.2019.02452	journal	October 2019
The Role of Structural Pleiotropy and Regulatory Evolution in the Retention of Heteromers of Paralogs Marchant, Axelle; Cisneros Caballero, Angel F.; Dubé, Alexandre K. Biophysical Journal, Vol. 118, Issue 3 https://doi.org/10.1016/j.bpj.2019.11.304	journal	February 2020
Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments Jackson, Christopher A.; Castro, Dayanne M.; Saldi, Giuseppe-Antonio eLife, Vol. 9 https://doi.org/10.7554/elife.51254	journal	January 2020
Leveraging transcriptional dynamics to improve BRAF inhibitor responses in melanoma Smalley, Inna; Kim, Eunjung; Li, Jiannong EBioMedicine, Vol. 48 https://doi.org/10.1016/j.ebiom.2019.09.023	journal	October 2019
Extrinsic Noise and Heavy-Tailed Laws in Gene Expression Ham, Lucy; Brackston, Rowan D.; Stumpf, Michael P. H. Physical Review Letters, Vol. 124, Issue 10 https://doi.org/10.1103/physrevlett.124.108101	journal	March 2020

Similar Records

Regulation of Yeast-to-Hyphae Transition in Yarrowia lipolytica

Journal Article · Wed Dec 26 00:00:00 EST 2018 · mSphere · OSTI ID:1499873

Pomraning, Kyle R.; Bredeweg, Erin L.; Kerkhoven, Eduard J.; +12 more

The rehydration transcriptome of the desiccation-tolerant bryophyte Tortula ruralis: transcript classification and analysis

Journal Article · Tue Nov 16 00:00:00 EST 2004 · BMC Genomics · OSTI ID:1499873

Oliver, Melvin J.; Dowd, Scot E.; Zaragoza, Joaquin; +2 more

Comparative transcriptome analysis of cells from different areas reveals ROS responsive mechanism at sclerotial initiation stage in Morchella importuna

Journal Article · Mon May 03 00:00:00 EDT 2021 · Scientific Reports · OSTI ID:1499873

Liu, Qizheng; He, Guoqiang; Wei, Jinkang; +1 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Title: Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress

Citation Formats

References (135)

Cited By (23)

Similar Records

Related Subjects