Origins of cell-to-cell bioprocessing diversity and implications of the extracellular environment revealed at the single-cell level

Vasdekis, A. E.; Silverman, A. M.; Stephanopoulos, G.

doi:10.1038/srep17689

Title: Origins of cell-to-cell bioprocessing diversity and implications of the extracellular environment revealed at the single-cell level

Journal Article · Mon Dec 14 00:00:00 EST 2015 · Scientific Reports

DOI:https://doi.org/10.1038/srep17689· OSTI ID:1259946

Vasdekis, A. E. ^[1]; Silverman, A. M. ^[2]; Stephanopoulos, G. ^[2]

Univ. of Idaho, Moscow, ID (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemical Engineering

We probed the lipid expression dynamics of the oleaginous yeast Yarrowia Lipolytica. We observed that neutral lipid expression is sporadic. By performing single-cell analysis, we found that such noise emanates from the metabolic reaction level. Our results provide an alternative insight into the regulation and phenotypic variability of lipogenesis.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-76RL01830; SC0008744

OSTI ID:: 1259946

Report Number(s):: PNNL-SA-110702; KP1704020

Journal Information:: Scientific Reports, Vol. 5; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 19 works

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References (38)

Challenges in Engineering Microbes for Biofuels Production Stephanopoulos, Gregory Science, Vol. 315, Issue 5813, p. 801-804 https://doi.org/10.1126/science.1139612	journal	February 2007
Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids Zhang, Fuzhong; Carothers, James M.; Keasling, Jay D. Nature Biotechnology, Vol. 30, Issue 4 https://doi.org/10.1038/nbt.2149	journal	March 2012
Microbial production of fatty-acid-derived fuels and chemicals from plant biomass Steen, Eric J.; Kang, Yisheng; Bokinsky, Gregory Nature, Vol. 463, Issue 7280, p. 559-562 https://doi.org/10.1038/nature08721	journal	January 2010
Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels Atsumi, Shota; Hanai, Taizo; Liao, James C. Nature, Vol. 451, Issue 7174, p. 86-89 https://doi.org/10.1038/nature06450	journal	January 2008
Engineering the push and pull of lipid biosynthesis in oleaginous yeast Yarrowia lipolytica for biofuel production Tai, Mitchell; Stephanopoulos, Gregory Metabolic Engineering, Vol. 15, p. 1-9 https://doi.org/10.1016/j.ymben.2012.08.007	journal	January 2013
Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production Blazeck, John; Hill, Andrew; Liu, Leqian Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4131	journal	January 2014
Stochasticity in gene expression: from theories to phenotypes Kærn, Mads; Elston, Timothy C.; Blake, William J. Nature Reviews Genetics, Vol. 6, Issue 6 https://doi.org/10.1038/nrg1615	journal	May 2005
Stochastic switching as a survival strategy in fluctuating environments Acar, Murat; Mettetal, Jerome T.; van Oudenaarden, Alexander Nature Genetics, Vol. 40, Issue 4 https://doi.org/10.1038/ng.110	journal	March 2008
Cellular Decision Making and Biological Noise: From Microbes to Mammals Balázsi, Gábor; van Oudenaarden, Alexander; Collins, James J. Cell, Vol. 144, Issue 6 https://doi.org/10.1016/j.cell.2011.01.030	journal	March 2011
General properties of transcriptional time series in Escherichia coli So, Lok-hang; Ghosh, Anandamohan; Zong, Chenghang Nature Genetics, Vol. 43, Issue 6 https://doi.org/10.1038/ng.821	journal	May 2011
Stochasticity, Bistability and the Wisdom of Crowds: A Model for Associative Learning in Genetic Regulatory Networks Sorek, Matan; Balaban, Nathalie Q.; Loewenstein, Yonatan PLoS Computational Biology, Vol. 9, Issue 8 https://doi.org/10.1371/journal.pcbi.1003179	journal	August 2013
Review of methods to probe single cell metabolism and bioenergetics Vasdekis, Andreas E.; Stephanopoulos, Gregory Metabolic Engineering, Vol. 27 https://doi.org/10.1016/j.ymben.2014.09.007	journal	January 2015
Cell-to-Cell Heterogeneity in Lipid Droplets Suggests a Mechanism to Reduce Lipotoxicity Herms, Albert; Bosch, Marta; Ariotti, Nicholas Current Biology, Vol. 23, Issue 15 https://doi.org/10.1016/j.cub.2013.06.032	journal	August 2013
Characterizing metabolic pathway diversification in the context of perturbation size Yang, Laurence; Srinivasan, Shyamsundhar; Mahadevan, Radhakrishnan Metabolic Engineering, Vol. 28 https://doi.org/10.1016/j.ymben.2014.11.013	journal	March 2015
Assessing the potential of mutational strategies to elicit new phenotypes in industrial strains Klein-Marcuschamer, D.; Stephanopoulos, G. Proceedings of the National Academy of Sciences, Vol. 105, Issue 7, p. 2319-2324 https://doi.org/10.1073/pnas.0712177105	journal	February 2008
Vesicle Photonics Vasdekis, A. E.; Scott, E. A.; Roke, S. Annual Review of Materials Research, Vol. 43, Issue 1 https://doi.org/10.1146/annurev-matsci-071312-121724	journal	July 2013
High Variation of Fluorescence Protein Maturation Times in Closely Related Escherichia coli Strains Hebisch, Elke; Knebel, Johannes; Landsberg, Janek PLoS ONE, Vol. 8, Issue 10 https://doi.org/10.1371/journal.pone.0075991	journal	October 2013
Single-Cell Metabolomics: Analytical and Biological Perspectives Zenobi, R. Science, Vol. 342, Issue 6163 https://doi.org/10.1126/science.1243259	journal	December 2013
The mechanical properties of Saccharomyces cerevisiae Smith, A. E.; Zhang, Z.; Thomas, C. R. Proceedings of the National Academy of Sciences, Vol. 97, Issue 18 https://doi.org/10.1073/pnas.97.18.9871	journal	August 2000
Stochastic Gene Expression in a Single Cell Elowitz, M. B. Science, Vol. 297, Issue 5584 https://doi.org/10.1126/science.1070919	journal	August 2002
Regulation of noise in the expression of a single gene Ozbudak, Ertugrul M.; Thattai, Mukund; Kurtser, Iren Nature Genetics, Vol. 31, Issue 1 https://doi.org/10.1038/ng869	journal	April 2002
Intrinsic and extrinsic contributions to stochasticity in gene expression Swain, P. S.; Elowitz, M. B.; Siggia, E. D. Proceedings of the National Academy of Sciences, Vol. 99, Issue 20 https://doi.org/10.1073/pnas.162041399	journal	September 2002
Predicting stochastic gene expression dynamics in single cells Mettetal, J. T.; Muzzey, D.; Pedraza, J. M. Proceedings of the National Academy of Sciences, Vol. 103, Issue 19 https://doi.org/10.1073/pnas.0509874103	journal	April 2006
Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences Raj, Arjun; van Oudenaarden, Alexander Cell, Vol. 135, Issue 2 https://doi.org/10.1016/j.cell.2008.09.050	journal	October 2008
Using Gene Expression Noise to Understand Gene Regulation Munsky, B.; Neuert, G.; van Oudenaarden, A. Science, Vol. 336, Issue 6078 https://doi.org/10.1126/science.1216379	journal	April 2012
Central dogma at the single-molecule level in living cells Li, Gene-Wei; Xie, X. Sunney Nature, Vol. 475, Issue 7356 https://doi.org/10.1038/nature10315	journal	July 2011
Stochasticity of metabolism and growth at the single-cell level Kiviet, Daniel J.; Nghe, Philippe; Walker, Noreen Nature, Vol. 514, Issue 7522 https://doi.org/10.1038/nature13582	journal	September 2014
Heterogeneity in protein expression induces metabolic variability in a modeled Escherichia coli population Labhsetwar, Piyush; Cole, John Andrew; Roberts, Elijah Proceedings of the National Academy of Sciences, Vol. 110, Issue 34 https://doi.org/10.1073/pnas.1222569110	journal	August 2013
Quantification of protein half-lives in the budding yeast proteome Belle, A.; Tanay, A.; Bitincka, L. Proceedings of the National Academy of Sciences, Vol. 103, Issue 35 https://doi.org/10.1073/pnas.0605420103	journal	August 2006
Engineering stability in gene networks by autoregulation Becskei, Attila; Serrano, Luis Nature, Vol. 405, Issue 6786 https://doi.org/10.1038/35014651	journal	June 2000
Heterogeneity in the physiological states and pharmacological responses of differentiating 3T3-L1 preadipocytes Loo, Lit-Hsin; Lin, Hai-Jui; Singh, Dinesh K. The Journal of Cell Biology, Vol. 187, Issue 3 https://doi.org/10.1083/jcb.200904140	journal	October 2009
Factors underlying the variability of lipid droplet fluorescence in MA-10 leydig tumor cells Gocze, Peter M.; Freeman, Dale A. Cytometry, Vol. 17, Issue 2 https://doi.org/10.1002/cyto.990170207	journal	October 1994
Single-cell NF-κB dynamics reveal digital activation and analogue information processing Tay, Savaş; Hughey, Jacob J.; Lee, Timothy K. Nature, Vol. 466, Issue 7303 https://doi.org/10.1038/nature09145	journal	June 2010
Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption Wang, Benjamin L.; Ghaderi, Adel; Zhou, Hang Nature Biotechnology, Vol. 32, Issue 5 https://doi.org/10.1038/nbt.2857	journal	April 2014
Microfluidic Large-Scale Integration Thorsen, T. Science, Vol. 298, Issue 5593 https://doi.org/10.1126/science.1076996	journal	September 2002
A trap-and-release integrated microfluidic system for dynamic microarray applications Tan, W.-H.; Takeuchi, S. Proceedings of the National Academy of Sciences, Vol. 104, Issue 4, p. 1146-1151 https://doi.org/10.1073/pnas.0606625104	journal	January 2007
Single microbe trap and release in sub-microfluidics Vasdekis, Andreas E. RSC Advances, Vol. 3, Issue 18 https://doi.org/10.1039/c3ra40369f	journal	January 2013
The Coefficient of Variation as an Index of Measurement Reliability Shechtman, Orit Springer Series on Epidemiology and Public Health https://doi.org/10.1007/978-3-642-37131-8_4	book	January 2013

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Microbial phenotypic heterogeneity in response to a metabolic toxin: Continuous, dynamically shifting distribution of formaldehyde tolerance in Methylobacterium extorquens populations Lee, Jessica A.; Riazi, Siavash; Nemati, Shahla PLOS Genetics, Vol. 15, Issue 11 https://doi.org/10.1371/journal.pgen.1008458	journal	November 2019
Heterogeneity in Pure Microbial Systems: Experimental Measurements and Modeling González-Cabaleiro, Rebeca; Mitchell, Anca M.; Smith, Wendy Frontiers in Microbiology, Vol. 8 https://doi.org/10.3389/fmicb.2017.01813	journal	September 2017
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