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. 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.
- Authors:
-
- 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); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1499873
- Alternate Identifier(s):
- OSTI ID: 1619084
- 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. 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.},
doi = {10.1371/journal.pbio.2004050},
journal = {PLoS Biology (Online)},
number = 12,
volume = 15,
place = {United States},
year = {2017},
month = {12}
}
Web of Science
Works referenced in this record:
Protein kinase A and TORC1 activate genes for ribosomal biogenesis by inactivating repressors encoded by Dot6 and its homolog Tod6
journal, November 2009
- Lippman, S. I.; Broach, J. R.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 47
Contributions of low molecule number and chromosomal positioning to stochastic gene expression
journal, August 2005
- Becskei, Attila; Kaufmann, Benjamin B.; van Oudenaarden, Alexander
- Nature Genetics, Vol. 37, Issue 9
Msn2 Coordinates a Stoichiometric Gene Expression Program
journal, December 2013
- Stewart-Ornstein, Jacob; Nelson, Christopher; DeRisi, Joe
- Current Biology, Vol. 23, Issue 23
SCnorm: robust normalization of single-cell RNA-seq data
journal, April 2017
- Bacher, Rhonda; Chu, Li-Fang; Leng, Ning
- Nature Methods, Vol. 14, Issue 6
Encoding four gene expression programs in the activation dynamics of a single transcription factor
journal, April 2016
- Hansen, Anders S.; O’Shea, Erin K.
- Current Biology, Vol. 26, Issue 7
p53 is a general repressor of RNA polymerase III transcription
journal, June 1998
- Cairns, C. A.
- The EMBO Journal, Vol. 17, Issue 11
Frequency-modulated nuclear localization bursts coordinate gene regulation
journal, September 2008
- Cai, Long; Dalal, Chiraj K.; Elowitz, Michael B.
- Nature, Vol. 455, Issue 7212
Proteasomal degradation of Sfp1 contributes to the repression of ribosome biogenesis during starvation and is mediated by the proteasome activator Blm10
journal, March 2011
- Lopez, Antonio Diaz; Tar, Krisztina; Krügel, Undine
- Molecular Biology of the Cell, Vol. 22, Issue 5
Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes
journal, June 2012
- Chymkowitch, P.; Eldholm, V.; Lorenz, S.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 26
Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance
journal, June 2017
- Shaffer, Sydney M.; Dunagin, Margaret C.; Torborg, Stefan R.
- Nature, Vol. 546, Issue 7658
Global analysis of protein expression in yeast
journal, October 2003
- Ghaemmaghami, Sina; Huh, Won-Ki; Bower, Kiowa
- Nature, Vol. 425, Issue 6959
Bacterial Persistence as a Phenotypic Switch
journal, September 2004
- Balaban, Nathalie Q.; Merrin, Jack; Chait, Remy
- Science, Vol. 305, Issue 5690, p. 1622-1625
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.
journal, June 1988
- Tsay, Y. F.; Thompson, J. R.; Rotenberg, M. O.
- Genes & Development, Vol. 2, Issue 6
Pathway connectivity and signaling coordination in the yeast stress‐activated signaling network
journal, November 2014
- Chasman, Deborah; Ho, Yi‐Hsuan; Berry, David B.
- Molecular Systems Biology, Vol. 10, Issue 11
Bet Hedging in Yeast by Heterogeneous, Age-Correlated Expression of a Stress Protectant
journal, May 2012
- Levy, Sasha F.; Ziv, Naomi; Siegal, Mark L.
- PLoS Biology, Vol. 10, Issue 5
Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation
journal, August 2008
- López-Maury, Luis; Marguerat, Samuel; Bähler, Jürg
- Nature Reviews Genetics, Vol. 9, Issue 8
Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
journal, June 2013
- Petrenko, Natalia; Chereji, Raˇzvan V.; McClean, Megan N.
- Molecular Biology of the Cell, Vol. 24, Issue 12
Fast and accurate long-read alignment with Burrows–Wheeler transform
journal, January 2010
- Li, Heng; Durbin, Richard
- Bioinformatics, Vol. 26, Issue 5
Methods of Digital Video Microscopy for Colloidal Studies
journal, April 1996
- Crocker, John C.; Grier, David G.
- Journal of Colloid and Interface Science, Vol. 179, Issue 1
Characterization of the p53 Cistrome – DNA Binding Cooperativity Dissects p53's Tumor Suppressor Functions
journal, August 2013
- Schlereth, Katharina; Heyl, Charlotte; Krampitz, Anna-Maria
- PLoS Genetics, Vol. 9, Issue 8
The importance of being persistent: heterogeneity of bacterial populations under antibiotic stress
journal, July 2009
- Gefen, Orit; Balaban, Nathalie Q.
- FEMS Microbiology Reviews, Vol. 33, Issue 4
Balanced Production of Ribosome Components Is Required for Proper G 1 /S Transition in Saccharomyces cerevisiae
journal, September 2013
- Gómez-Herreros, Fernando; Rodríguez-Galán, Olga; Morillo-Huesca, Macarena
- Journal of Biological Chemistry, Vol. 288, Issue 44
Characterizing transcriptional heterogeneity through pathway and gene set overdispersion analysis
journal, January 2016
- Fan, Jean; Salathia, Neeraj; Liu, Rui
- Nature Methods, Vol. 13, Issue 3
Multiple Means to the Same End: The Genetic Basis of Acquired Stress Resistance in Yeast
journal, November 2011
- Berry, David B.; Guan, Qiaoning; Hose, James
- PLoS Genetics, Vol. 7, Issue 11
Cell cycle Start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates
journal, January 2016
- Burnetti, Anthony J.; Aydin, Mert; Buchler, Nicolas E.
- Molecular Biology of the Cell, Vol. 27, Issue 1
Remodeling of Yeast Genome Expression in Response to Environmental Changes
journal, February 2001
- Causton, Helen C.; Ren, Bing; Koh, Sang Seok
- Molecular Biology of the Cell, Vol. 12, Issue 2
Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression
journal, October 2015
- Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A.; Ilicic, Tomislav
- Nature Communications, Vol. 6, Issue 1
Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism and Cell Cycle in S. cerevisiae
journal, May 2016
- Zhao, Gang; Chen, Yuping; Carey, Lucas
- Molecular Cell, Vol. 62, Issue 4
Noise in Gene Expression: Origins, Consequences, and Control
journal, September 2005
- Raser, J. M.
- Science, Vol. 309, Issue 5743
Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1
journal, October 1998
- Ferrigno, P.
- The EMBO Journal, Vol. 17, Issue 19
The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression
journal, May 2016
- Ewald, Jennifer C.; Kuehne, Andreas; Zamboni, Nicola
- Molecular Cell, Vol. 62, Issue 4
Cluster analysis and display of genome-wide expression patterns
journal, December 1998
- Eisen, M. B.; Spellman, P. T.; Brown, P. O.
- Proceedings of the National Academy of Sciences, Vol. 95, Issue 25
Cellular Heterogeneity: Benefits Besides Bet-Hedging
journal, May 2016
- Levy, Sasha F.
- Current Biology, Vol. 26, Issue 9
Hog1 Targets Whi5 and Msa1 Transcription Factors To Downregulate Cyclin Expression upon Stress
journal, March 2015
- González-Novo, Alberto; Jiménez, Javier; Clotet, Josep
- Molecular and Cellular Biology, Vol. 35, Issue 9
Metabolic cycling in single yeast cells from unsynchronized steady-state populations limited on glucose or phosphate
journal, March 2010
- Silverman, S. J.; Petti, A. A.; Slavov, N.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 15
Fiji: an open-source platform for biological-image analysis
journal, June 2012
- Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin
- Nature Methods, Vol. 9, Issue 7
Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators Msn2 and Msn4 in Saccharomyces cerevisiae
journal, May 2003
- Jacquet, Michel; Renault, Georges; Lallet, Sylvie
- The Journal of Cell Biology, Vol. 161, Issue 3
Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling
journal, May 2015
- Ho, Yi-Hsuan; Gasch, Audrey P.
- Current Genetics, Vol. 61, Issue 4
Up-to-date catalogues of yeast protein complexes
journal, December 2008
- Pu, Shuye; Wong, Jessica; Turner, Brian
- Nucleic Acids Research, Vol. 37, Issue 3
Chromatin decouples promoter threshold from dynamic range
journal, April 2008
- Lam, Felix H.; Steger, David J.; O’Shea, Erin K.
- Nature, Vol. 453, Issue 7192
Ribosome Biogenesis Is Sensed at the Start Cell Cycle Checkpoint
journal, March 2007
- Bernstein, Kara A.; Bleichert, Franziska; Bean, James M.
- Molecular Biology of the Cell, Vol. 18, Issue 3
Regulated cell-to-cell variation in a cell-fate decision system
journal, September 2005
- Colman-Lerner, Alejandro; Gordon, Andrew; Serra, Eduard
- Nature, Vol. 437, Issue 7059
Promoter decoding of transcription factor dynamics involves a trade‐off between noise and control of gene expression
journal, January 2013
- Hansen, Anders S.; O'Shea, Erin K.
- Molecular Systems Biology, Vol. 9, Issue 1
The role of physiological heterogeneity in microbial population behavior
journal, September 2010
- Lidstrom, Mary E.; Konopka, Michael C.
- Nature Chemical Biology, Vol. 6, Issue 10
Schedule-dependent interaction between anticancer treatments
journal, March 2016
- Chen, Sheng-hong; Forrester, William; Lahav, Galit
- Science, Vol. 351, Issue 6278
Signal-dependent dynamics of transcription factor translocation controls gene expression
journal, December 2011
- Hao, Nan; O'Shea, Erin K.
- Nature Structural & Molecular Biology, Vol. 19, Issue 1
The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress
journal, January 2009
- Alejandro-Osorio, Adriana L.; Huebert, Dana J.; Porcaro, Dominic T.
- Genome Biology, Vol. 10, Issue 5
Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization
journal, December 1998
- Spellman, Paul T.; Sherlock, Gavin; Zhang, Michael Q.
- Molecular Biology of the Cell, Vol. 9, Issue 12
Identification and Distinct Regulation of Yeast TATA Box-Containing Genes
journal, March 2004
- Basehoar, Andrew D.; Zanton, Sara J.; Pugh, B. Franklin
- Cell, Vol. 116, Issue 5
Growth control and ribosome biogenesis
journal, December 2009
- Lempiäinen, Harri; Shore, David
- Current Opinion in Cell Biology, Vol. 21, Issue 6
Sfp1 Plays a Key Role in Yeast Ribosome Biogenesis
journal, October 2003
- Fingerman, Ian; Nagaraj, Vijayalakshmi; Norris, David
- Eukaryotic Cell, Vol. 2, Issue 5
Exploiting Natural Variation in Saccharomyces cerevisiae to Identify Genes for Increased Ethanol Resistance
journal, September 2010
- Lewis, Jeffrey A.; Elkon, Isaac M.; McGee, Mick A.
- Genetics, Vol. 186, Issue 4
Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity
journal, February 1998
- Gorner, W.; Durchschlag, E.; Martinez-Pastor, M. T.
- Genes & Development, Vol. 12, Issue 4
Coupling among growth rate response, metabolic cycle, and cell division cycle in yeast
journal, June 2011
- Slavov, Nikolai; Botstein, David
- Molecular Biology of the Cell, Vol. 22, Issue 12
Slow-Cycling Therapy-Resistant Cancer Cells
journal, July 2012
- Moore, Nathan; Houghton, JeanMarie; Lyle, Stephen
- Stem Cells and Development, Vol. 21, Issue 10
Dynamic Changes in Nucleosome Occupancy Are Not Predictive of Gene Expression Dynamics but Are Linked to Transcription and Chromatin Regulators
journal, February 2012
- Huebert, D. J.; Kuan, P. -F.; Keles, S.
- Molecular and Cellular Biology, Vol. 32, Issue 9
Slow Growth Induces Heat-Shock Resistance in Normal and Respiratory-deficient Yeast
journal, February 2009
- Lu, Charles; Brauer, Matthew J.; Botstein, David
- Molecular Biology of the Cell, Vol. 20, Issue 3
Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage
journal, August 2015
- van Dijk, David; Dhar, Riddhiman; Missarova, Alsu M.
- Nature Communications, Vol. 6, Issue 1
Classification of low quality cells from single-cell RNA-seq data
journal, February 2016
- Ilicic, Tomislav; Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A.
- Genome Biology, Vol. 17, Issue 1
Pulsatile Dynamics in the Yeast Proteome
journal, September 2014
- Dalal, Chiraj K.; Cai, Long; Lin, Yihan
- Current Biology, Vol. 24, Issue 18
Single-Cell Analysis Reveals That Insulation Maintains Signaling Specificity Between Two Yeast MAPK Pathways with Common Components
journal, October 2010
- Patterson, J. C.; Klimenko, E. S.; Thorner, J.
- Science Signaling, Vol. 3, Issue 144
Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm
journal, August 2016
- Chu, Li-Fang; Leng, Ning; Zhang, Jue
- Genome Biology, Vol. 17, Issue 1
Transcriptional Regulation by P53
journal, April 2010
- Beckerman, R.; Prives, C.
- Cold Spring Harbor Perspectives in Biology, Vol. 2, Issue 8
YEASTRACT: providing a programmatic access to curated transcriptional regulatory associations in Saccharomyces cerevisiae through a web services interface
journal, October 2010
- Abdulrehman, D.; Monteiro, P. T.; Teixeira, M. C.
- Nucleic Acids Research, Vol. 39, Issue Database
Batch effects and the effective design of single-cell gene expression studies
journal, January 2017
- Tung, Po-Yuan; Blischak, John D.; Hsiao, Chiaowen Joyce
- Scientific Reports, Vol. 7, Issue 1
Cellular Noise Regulons Underlie Fluctuations in Saccharomyces cerevisiae
journal, February 2012
- Stewart-Ornstein, Jacob; Weissman, Jonathan S.; El-Samad, Hana
- Molecular Cell, Vol. 45, Issue 4
p53 Dynamics Control Cell Fate
journal, June 2012
- Purvis, J. E.; Karhohs, K. W.; Mock, C.
- Science, Vol. 336, Issue 6087
Cell cycle population effects in perturbation studies
journal, June 2014
- O'Duibhir, Eoghan; Lijnzaad, Philip; Benschop, Joris J.
- Molecular Systems Biology, Vol. 10, Issue 6
Quantification of the yeast transcriptome by single-molecule sequencing
journal, July 2009
- Lipson, Doron; Raz, Tal; Kieu, Alix
- Nature Biotechnology, Vol. 27, Issue 7
Single-RNA counting reveals alternative modes of gene expression in yeast
journal, November 2008
- Zenklusen, Daniel; Larson, Daniel R.; Singer, Robert H.
- Nature Structural & Molecular Biology, Vol. 15, Issue 12
Growth control of the eukaryote cell: a systems biology study in yeast
journal, January 2007
- Castrillo, Juan I.; Zeef, Leo A.; Hoyle, David C.
- Journal of Biology, Vol. 6, Issue 2
The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors
journal, December 1999
- Beck, Thomas; Hall, Michael N.
- Nature, Vol. 402, Issue 6762
Affinity and competition for TBP are molecular determinants of gene expression noise
journal, February 2016
- Ravarani, Charles N. J.; Chalancon, Guilhem; Breker, Michal
- Nature Communications, Vol. 7, Issue 1
Control of Stochasticity in Eukaryotic Gene Expression
journal, June 2004
- Raser, J. M.
- Science, Vol. 304, Issue 5678
Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor
journal, January 2002
- Gorner, W.
- The EMBO Journal, Vol. 21, Issue 1
Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise
journal, May 2006
- Newman, John R. S.; Ghaemmaghami, Sina; Ihmels, Jan
- Nature, Vol. 441, Issue 7095
Phenotypic Consequences of Promoter-Mediated Transcriptional Noise
journal, December 2006
- Blake, William J.; Balázsi, Gábor; Kohanski, Michael A.
- Molecular Cell, Vol. 24, Issue 6
Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation
journal, July 1998
- Smith, A.
- The EMBO Journal, Vol. 17, Issue 13
Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L
journal, July 2011
- Huber, Alexandre; French, Sarah L.; Tekotte, Hille
- The EMBO Journal, Vol. 30, Issue 15
Transcriptional regulatory code of a eukaryotic genome
journal, September 2004
- Harbison, Christopher T.; Gordon, D. Benjamin; Lee, Tong Ihn
- Nature, Vol. 431, Issue 7004
Ribosomal protein L32 of Saccharomyces cerevisiae influences both the splicing of its own transcript and the processing of rRNA.
journal, April 1997
- Vilardell, J.; Warner, J. R.
- Molecular and Cellular Biology, Vol. 17, Issue 4
A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor Growth
journal, May 2010
- Roesch, Alexander; Fukunaga-Kalabis, Mizuho; Schmidt, Elizabeth C.
- Cell, Vol. 141, Issue 4
Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity.
journal, March 1994
- Klein, C.; Struhl, K.
- Molecular and Cellular Biology, Vol. 14, Issue 3
Noise in protein expression scales with natural protein abundance
journal, May 2006
- Bar-Even, Arren; Paulsson, Johan; Maheshri, Narendra
- Nature Genetics, Vol. 38, Issue 6
Combinatorial gene regulation by modulation of relative pulse timing
journal, October 2015
- Lin, Yihan; Sohn, Chang Ho; Dalal, Chiraj K.
- Nature, Vol. 527, Issue 7576
Logic of the Yeast Metabolic Cycle: Temporal Compartmentalization of Cellular Processes
journal, November 2005
- Tu, B. P.
- Science, Vol. 310, Issue 5751
Poised epigenetic states and acquired drug resistance in cancer
journal, September 2014
- Brown, Robert; Curry, Edward; Magnani, Luca
- Nature Reviews Cancer, Vol. 14, Issue 11
Comparative Analysis of Single-Cell RNA Sequencing Methods
journal, February 2017
- Ziegenhain, Christoph; Vieth, Beate; Parekh, Swati
- Molecular Cell, Vol. 65, Issue 4
Molecular mechanisms of ribosomal protein gene coregulation
journal, September 2015
- Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana
- Genes & Development, Vol. 29, Issue 18
A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
journal, April 2010
- Sharma, Sreenath V.; Lee, Diana Y.; Li, Bihua
- Cell, Vol. 141, Issue 1
Stress-activated Genomic Expression Changes Serve a Preparative Role for Impending Stress in Yeast
journal, November 2008
- Berry, David B.; Gasch, Audrey P.
- Molecular Biology of the Cell, Vol. 19, Issue 11
Bayesian approach to single-cell differential expression analysis
journal, May 2014
- Kharchenko, Peter V.; Silberstein, Lev; Scadden, David T.
- Nature Methods, Vol. 11, Issue 7
Autonomous Metabolic Oscillations Robustly Gate the Early and Late Cell Cycle
journal, January 2017
- Papagiannakis, Alexandros; Niebel, Bastian; Wit, Ernst C.
- Molecular Cell, Vol. 65, Issue 2
From single-cell to cell-pool transcriptomes: Stochasticity in gene expression and RNA splicing
journal, December 2013
- Marinov, G. K.; Williams, B. A.; McCue, K.
- Genome Research, Vol. 24, Issue 3
cis Determinants of Promoter Threshold and Activation Timescale
journal, August 2015
- Hansen, Anders S.; O’Shea, Erin K.
- Cell Reports, Vol. 12, Issue 8
Saccharomyces cerevisiae coordinates accumulation of yeast ribosomal proteins by modulating mRNA splicing, translational initiation, and protein turnover.
journal, June 1985
- Warner, J. R.; Mitra, G.; Schwindinger, W. F.
- Molecular and Cellular Biology, Vol. 5, Issue 6
Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression
journal, September 2004
- Marion, R. M.; Regev, A.; Segal, E.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 40
p53 represses ribosomal gene transcription
journal, January 1999
- Budde, Andreja; Grummt, Ingrid
- Oncogene, Vol. 18, Issue 4
Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes
journal, December 2000
- Gasch, Audrey P.; Spellman, Paul T.; Kao, Camilla M.
- Molecular Biology of the Cell, Vol. 11, Issue 12
High-resolution DNA-binding specificity analysis of yeast transcription factors
journal, January 2009
- Zhu, C.; Byers, K. J. R. P.; McCord, R. P.
- Genome Research, Vol. 19, Issue 4
Genomic Expression Responses to DNA-damaging Agents and the Regulatory Role of the Yeast ATR Homolog Mec1p
journal, October 2001
- Gasch, Audrey P.; Huang, Mingxia; Metzner, Sandra
- Molecular Biology of the Cell, Vol. 12, Issue 10
Homeostatic Adjustment and Metabolic Remodeling in Glucose-limited Yeast Cultures
journal, May 2005
- Brauer, Matthew J.; Saldanha, Alok J.; Dolinski, Kara
- Molecular Biology of the Cell, Vol. 16, Issue 5
Tunable Signal Processing Through Modular Control of Transcription Factor Translocation
journal, January 2013
- Hao, N.; Budnik, B. A.; Gunawardena, J.
- Science, Vol. 339, Issue 6118
A Comprehensive Genomic Binding Map of Gene and Chromatin Regulatory Proteins in Saccharomyces
journal, February 2011
- Venters, Bryan J.; Wachi, Shinichiro; Mavrich, Travis N.
- Molecular Cell, Vol. 41, Issue 4
Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq experiments
journal, August 2015
- Leng, Ning; Chu, Li-Fang; Barry, Chris
- Nature Methods, Vol. 12, Issue 10
Dynamic control of gene regulatory logic by seemingly redundant transcription factors
journal, September 2016
- AkhavanAghdam, Zohreh; Sinha, Joydeb; Tabbaa, Omar P.
- eLife, Vol. 5
Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1
journal, September 2004
- Escoté, Xavier; Zapater, Meritxell; Clotet, Josep
- Nature Cell Biology, Vol. 6, Issue 10
A Systems-Level Analysis of Perfect Adaptation in Yeast Osmoregulation
journal, July 2009
- Muzzey, Dale; Gómez-Uribe, Carlos A.; Mettetal, Jerome T.
- Cell, Vol. 138, Issue 1
Nucleocytoplasmic Oscillations of the Yeast Transcription Factor Msn2: Evidence for Periodic PKA Activation
journal, June 2007
- Garmendia-Torres, Cecilia; Goldbeter, Albert; Jacquet, Michel
- Current Biology, Vol. 17, Issue 12
Persistence to anti-cancer treatments in the stationary to proliferating transition
journal, October 2016
- Pearl Mizrahi, Sivan; Gefen, Orit; Simon, Itamar
- Cell Cycle, Vol. 15, Issue 24
Saccharomyces Genome Database: the genomics resource of budding yeast
journal, November 2011
- Cherry, J. M.; Hong, E. L.; Amundsen, C.
- Nucleic Acids Research, Vol. 40, Issue D1
Imaging individual mRNA molecules using multiple singly labeled probes
journal, September 2008
- Raj, Arjun; van den Bogaard, Patrick; Rifkin, Scott A.
- Nature Methods, Vol. 5, Issue 10
Commitment to a Cellular Transition Precedes Genome-wide Transcriptional Change
journal, August 2011
- Eser, Umut; Falleur-Fettig, Melody; Johnson, Amy
- Molecular Cell, Vol. 43, Issue 4
TOR Regulates Ribosomal Protein Gene Expression via PKA and the Forkhead Transcription Factor FHL1
journal, December 2004
- Martin, Dietmar E.; Soulard, Alexandre; Hall, Michael N.
- Cell, Vol. 119, Issue 7
Basal Dynamics of p53 Reveal Transcriptionally Attenuated Pulses in Cycling Cells
journal, July 2010
- Loewer, Alexander; Batchelor, Eric; Gaglia, Giorgio
- Cell, Vol. 142, Issue 1
Works referencing / citing this record:
Single-Cell RNA Sequencing-Based Computational Analysis to Describe Disease Heterogeneity
journal, July 2019
- Zeng, Tao; Dai, Hao
- Frontiers in Genetics, Vol. 10
Distributed and dynamic intracellular organization of extracellular information
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- Granados, Alejandro A.; Pietsch, Julian M. J.; Cepeda-Humerez, Sarah A.
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 23
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- Ma, Qin; Bücking, Heike; Gonzalez Hernandez, Jose L.
- Frontiers in Microbiology, Vol. 10
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- Ma, Qin; Bücking, Heike; Gonzalez Hernandez, Jose L.
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journal, July 2019
- Zeng, Tao; Dai, Hao
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journal, May 2018
- Granados, Alejandro A.; Pietsch, Julian M. J.; Cepeda-Humerez, Sarah A.
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 23
Extrinsic Noise and Heavy-Tailed Laws in Gene Expression
journal, March 2020
- Ham, Lucy; Brackston, Rowan D.; Stumpf, Michael P. H.
- Physical Review Letters, Vol. 124, Issue 10
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journal, February 2019
- Saint, Malika; Bertaux, François; Tang, Wenhao
- Nature Microbiology, Vol. 4, Issue 3
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journal, February 2019
- Nadal-Ribelles, Mariona; Islam, Saiful; Wei, Wu
- Nature Microbiology, Vol. 4, Issue 4
High throughput gene expression profiling of yeast colonies with microgel-culture Drop-seq
journal, January 2019
- Liu, Leqian; Dalal, Chiraj K.; Heineike, Benjamin M.
- Lab on a Chip, Vol. 19, Issue 10
Complex genetic and epigenetic regulation deviates gene expression from a unifying global transcriptional program
journal, September 2019
- Chagoyen, Mónica; Poyatos, Juan F.
- PLOS Computational Biology, Vol. 15, Issue 9
Control of nongenetic heterogeneity in growth rate and stress tolerance of Saccharomyces cerevisiae by cyclic AMP-regulated transcription factors
journal, November 2018
- Li, Shuang; Giardina, Daniella M.; Siegal, Mark L.
- PLOS Genetics, Vol. 14, Issue 11
Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging
journal, December 2019
- Walzer, Katelyn A.; Fradin, Hélène; Emerson, Liane Y.
- PLOS Genetics, Vol. 15, Issue 12
Widespread inter‐individual gene expression variability in Arabidopsis thaliana
journal, January 2019
- Cortijo, Sandra; Aydin, Zeynep; Ahnert, Sebastian
- Molecular Systems Biology, Vol. 15, Issue 1