Single-Cell Metabolic Profiling: Metabolite Formulas from Isotopic Fine Structures in Heterogeneous Plant Cell Populations
Abstract
Characterization of the metabolic heterogeneity in cell populations requires the analysis of single cells. Most current methods in single-cell analysis rely on cell manipulation, potentially altering the abundance of metabolites in individual cells. Small sample volume and the chemical diversity of metabolites are additional challenges in single-cell metabolomics. Here, we describe the combination of fiber-based laser ablation electrospray ionization (f-LAESI) with 21 tesla Fourier transform ion cyclotron resonance mass spectrometry (21TFTICR-MS) for in situ single-cell metabolic profiling in plant tissue. Single plant cells infected by bacteria were selected and sampled directly from the tissue without cell manipulation through mid-infrared ablation with a fine optical fiber tip for ionization by f-LAESI. Finally, ultrahigh performance 21T-FTICR-MS enabled the simultaneous capture of isotopic fine structures (IFSs) for 47 known and 11 unknown compounds, thus elucidating their elemental compositions from single cells, and providing information on metabolic heterogeneity in the cell population.
- Authors:
-
[1];
[2];
[2];
[2];
[1]
- George Washington Univ., Washington, DC (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
- Univ. of Missouri, Columbia, MO (United States)
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); George Washington Univ., Washington, DC (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF)
- OSTI Identifier:
- 1647344
- Alternate Identifier(s):
- OSTI ID: 1615474
- Report Number(s):
- PNNL-SA-152789
Journal ID: ISSN 0003-2700
- Grant/Contract Number:
- AC05-76RL01830; SC0013978; IoS-1734145
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Analytical Chemistry
- Additional Journal Information:
- Journal Volume: 92; Journal Issue: 10; Journal ID: ISSN 0003-2700
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; plants, infectious diseases, fibers, metabolism, ions
Citation Formats
Samarah, Laith Z., Khattar, Rikkita, Tran, Tina H., Stopka, Sylwia A., Brantner, Christine A., Parlanti, Paola, Veličković, Dušan, Shaw, Jared B., Agtuca, Beverly J., Stacey, Gary, Paša-Tolić, Ljiljana, Tolić, Nikola, Anderton, Christopher R., and Vertes, Akos. Single-Cell Metabolic Profiling: Metabolite Formulas from Isotopic Fine Structures in Heterogeneous Plant Cell Populations. United States: N. p., 2020.
Web. doi:10.1021/acs.analchem.0c00936.
Samarah, Laith Z., Khattar, Rikkita, Tran, Tina H., Stopka, Sylwia A., Brantner, Christine A., Parlanti, Paola, Veličković, Dušan, Shaw, Jared B., Agtuca, Beverly J., Stacey, Gary, Paša-Tolić, Ljiljana, Tolić, Nikola, Anderton, Christopher R., & Vertes, Akos. Single-Cell Metabolic Profiling: Metabolite Formulas from Isotopic Fine Structures in Heterogeneous Plant Cell Populations. United States. https://doi.org/10.1021/acs.analchem.0c00936
Samarah, Laith Z., Khattar, Rikkita, Tran, Tina H., Stopka, Sylwia A., Brantner, Christine A., Parlanti, Paola, Veličković, Dušan, Shaw, Jared B., Agtuca, Beverly J., Stacey, Gary, Paša-Tolić, Ljiljana, Tolić, Nikola, Anderton, Christopher R., and Vertes, Akos. Tue .
"Single-Cell Metabolic Profiling: Metabolite Formulas from Isotopic Fine Structures in Heterogeneous Plant Cell Populations". United States. https://doi.org/10.1021/acs.analchem.0c00936. https://www.osti.gov/servlets/purl/1647344.
@article{osti_1647344,
title = {Single-Cell Metabolic Profiling: Metabolite Formulas from Isotopic Fine Structures in Heterogeneous Plant Cell Populations},
author = {Samarah, Laith Z. and Khattar, Rikkita and Tran, Tina H. and Stopka, Sylwia A. and Brantner, Christine A. and Parlanti, Paola and Veličković, Dušan and Shaw, Jared B. and Agtuca, Beverly J. and Stacey, Gary and Paša-Tolić, Ljiljana and Tolić, Nikola and Anderton, Christopher R. and Vertes, Akos},
abstractNote = {Characterization of the metabolic heterogeneity in cell populations requires the analysis of single cells. Most current methods in single-cell analysis rely on cell manipulation, potentially altering the abundance of metabolites in individual cells. Small sample volume and the chemical diversity of metabolites are additional challenges in single-cell metabolomics. Here, we describe the combination of fiber-based laser ablation electrospray ionization (f-LAESI) with 21 tesla Fourier transform ion cyclotron resonance mass spectrometry (21TFTICR-MS) for in situ single-cell metabolic profiling in plant tissue. Single plant cells infected by bacteria were selected and sampled directly from the tissue without cell manipulation through mid-infrared ablation with a fine optical fiber tip for ionization by f-LAESI. Finally, ultrahigh performance 21T-FTICR-MS enabled the simultaneous capture of isotopic fine structures (IFSs) for 47 known and 11 unknown compounds, thus elucidating their elemental compositions from single cells, and providing information on metabolic heterogeneity in the cell population.},
doi = {10.1021/acs.analchem.0c00936},
journal = {Analytical Chemistry},
number = 10,
volume = 92,
place = {United States},
year = {Tue Apr 21 00:00:00 EDT 2020},
month = {Tue Apr 21 00:00:00 EDT 2020}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 29 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Cellular Heterogeneity: Do Differences Make a Difference?
journal, May 2010
- Altschuler, Steven J.; Wu, Lani F.
- Cell, Vol. 141, Issue 4
Single-Cell Metabolomics: Analytical and Biological Perspectives
journal, December 2013
- Zenobi, R.
- Science, Vol. 342, Issue 6163
Single-cell metabolomics comes of age: new developments in mass spectrometry profiling and imaging
journal, July 2011
- Svatoš, Aleš
- Analytical Chemistry, Vol. 83, Issue 13
Single-Cell Mass Spectrometry Approaches to Explore Cellular Heterogeneity
journal, March 2018
- Zhang, Linwen; Vertes, Akos
- Angewandte Chemie International Edition, Vol. 57, Issue 17
21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Greatly Expands Mass Spectrometry Toolbox
journal, October 2016
- Shaw, Jared B.; Lin, Tzu-Yung; Leach, Franklin E.
- Journal of The American Society for Mass Spectrometry, Vol. 27, Issue 12
Petroleomics: Chemistry of the underworld
journal, October 2008
- Marshall, A. G.; Rodgers, R. P.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 47
Advanced Solvent Based Methods for Molecular Characterization of Soil Organic Matter by High-Resolution Mass Spectrometry
journal, April 2015
- Tfaily, Malak M.; Chu, Rosalie K.; Tolić, Nikola
- Analytical Chemistry, Vol. 87, Issue 10
Chemical characterization of dissolved organic matter in moist acidic tussock tundra soil using ultra-high resolution 15T FT-ICR mass spectrometry
journal, September 2017
- Choi, Jung Hoon; Kim, Yun-Gon; Lee, Yoo Kyung
- Biotechnology and Bioprocess Engineering, Vol. 22, Issue 5
126 264 Assigned Chemical Formulas from an Atmospheric Pressure Photoionization 9.4 T Fourier Transform Positive Ion Cyclotron Resonance Mass Spectrum
journal, October 2017
- Krajewski, Logan C.; Rodgers, Ryan P.; Marshall, Alan G.
- Analytical Chemistry, Vol. 89, Issue 21
Identification and Characterization of Human Proteoforms by Top-Down LC-21 Tesla FT-ICR Mass Spectrometry
journal, December 2016
- Anderson, Lissa C.; DeHart, Caroline J.; Kaiser, Nathan K.
- Journal of Proteome Research, Vol. 16, Issue 2
Ambient Metabolic Profiling and Imaging of Biological Samples with Ultrahigh Molecular Resolution Using Laser Ablation Electrospray Ionization 21 Tesla FTICR Mass Spectrometry
journal, February 2019
- Stopka, Sylwia A.; Samarah, Laith Z.; Shaw, Jared B.
- Analytical Chemistry, Vol. 91, Issue 8
Comparative Analysis of Single-Cell RNA Sequencing Methods
journal, February 2017
- Ziegenhain, Christoph; Vieth, Beate; Parekh, Swati
- Molecular Cell, Vol. 65, Issue 4
Microsampling Capillary Electrophoresis Mass Spectrometry Enables Single-Cell Proteomics in Complex Tissues: Developing Cell Clones in Live Xenopus laevis and Zebrafish Embryos
journal, February 2019
- Lombard-Banek, Camille; Moody, Sally A.; Manzini, M. Chiara
- Analytical Chemistry, Vol. 91, Issue 7
Proteomic Analysis of Single Mammalian Cells Enabled by Microfluidic Nanodroplet Sample Preparation and Ultrasensitive NanoLC-MS
journal, June 2018
- Zhu, Ying; Clair, Geremy; Chrisler, William B.
- Angewandte Chemie International Edition, Vol. 57, Issue 38
Isolation of rare circulating tumour cells in cancer patients by microchip technology
journal, December 2007
- Nagrath, Sunitha; Sequist, Lecia V.; Maheswaran, Shyamala
- Nature, Vol. 450, Issue 7173
Catch and Release: rare cell analysis from a functionalised medical wire
journal, February 2017
- Chen, Shukun; El-Heliebi, Amin; Tauber, Gerlinde
- Scientific Reports, Vol. 7, Issue 1
Legume nodule organogenesis
journal, March 1998
- Cohn, Jonathan; Bradley Day, R.; Stacey, Gary
- Trends in Plant Science, Vol. 3, Issue 3
In Situ Metabolic Profiling of Single Cells by Laser Ablation Electrospray Ionization Mass Spectrometry
journal, October 2009
- Shrestha, Bindesh; Vertes, Akos
- Analytical Chemistry, Vol. 81, Issue 20
In Situ Cell-by-Cell Imaging and Analysis of Small Cell Populations by Mass Spectrometry
journal, April 2011
- Shrestha, Bindesh; Patt, Joseph M.; Vertes, Akos
- Analytical Chemistry, Vol. 83, Issue 8
Transmissible Resistance to Penicillin G, Neomycin, and Chloramphenicol in Rhizobium japonicum
journal, September 1973
- Cole, M. A.; Elkan, G. H.
- Antimicrobial Agents and Chemotherapy, Vol. 4, Issue 3
Laser-ablation electrospray ionization mass spectrometry with ion mobility separation reveals metabolites in the symbiotic interactions of soybean roots and rhizobia
journal, May 2017
- Stopka, Sylwia A.; Agtuca, Beverly J.; Koppenaal, David W.
- The Plant Journal, Vol. 91, Issue 2
Efficient Calculation of Exact Fine Structure Isotope Patterns via the Multidimensional Fourier Transform
journal, May 2014
- Ipsen, Andreas
- Analytical Chemistry, Vol. 86, Issue 11
Rapid Calculation of Isotope Distributions
journal, August 1995
- Rockwood, Alan L.; Van Orden, Steven L.; Smith, Richard D.
- Analytical Chemistry, Vol. 67, Issue 15
Ultrahigh Resolution Isotope Distribution Calculations
journal, January 1996
- Rockwood, Alan L.; Van Orden, Steven L.; Smith, Richard D.
- Rapid Communications in Mass Spectrometry, Vol. 10, Issue 1
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
journal, September 2005
- Subramanian, A.; Tamayo, P.; Mootha, V. K.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550
Fourier Transform Ion Cyclotron Resonance Mass Resolution and Dynamic Range Limits Calculated by Computer Modeling of Ion Cloud Motion
journal, October 2011
- Vladimirov, Gleb; Hendrickson, Christopher L.; Blakney, Greg T.
- Journal of The American Society for Mass Spectrometry, Vol. 23, Issue 2
Formularity: Software for Automated Formula Assignment of Natural and Other Organic Matter from Ultrahigh-Resolution Mass Spectra
journal, November 2017
- Tolić, Nikola; Liu, Yina; Liyu, Andrey
- Analytical Chemistry, Vol. 89, Issue 23
Structural resolution of carbohydrate positional and structural isomers based on gas-phase ion mobility-mass spectrometry
journal, January 2011
- Fenn, Larissa S.; McLean, John A.
- Phys. Chem. Chem. Phys., Vol. 13, Issue 6
Characterization of applied fields for ion mobility separations in traveling wave based structures for lossless ion manipulations (SLIM)
journal, July 2018
- Hamid, Ahmed M.; Prabhakaran, Aneesh; Garimella, Sandilya V. B.
- International Journal of Mass Spectrometry, Vol. 430
The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics
journal, March 2014
- Lanucara, Francesco; Holman, Stephen W.; Gray, Christopher J.
- Nature Chemistry, Vol. 6, Issue 4
High-Throughput Cell and Tissue Analysis with Enhanced Molecular Coverage by Laser Ablation Electrospray Ionization Mass Spectrometry Using Ion Mobility Separation
journal, April 2014
- Shrestha, Bindesh; Vertes, Akos
- Analytical Chemistry, Vol. 86, Issue 9
Ion Mobility-Derived Collision Cross Section As an Additional Measure for Lipid Fingerprinting and Identification
journal, December 2014
- Paglia, Giuseppe; Angel, Peggi; Williams, Jonathan P.
- Analytical Chemistry, Vol. 87, Issue 2
Ion Mobility Derived Collision Cross Sections to Support Metabolomics Applications
journal, March 2014
- Paglia, Giuseppe; Williams, Jonathan P.; Menikarachchi, Lochana
- Analytical Chemistry, Vol. 86, Issue 8
Infrared multiple photon dissociation (IRMPD) spectroscopy of oxazine dyes
journal, January 2013
- Nieckarz, Robert J.; Oomens, Jos; Berden, Giel
- Physical Chemistry Chemical Physics, Vol. 15, Issue 14
Infrared multiple photon dissociation spectroscopy of trapped ions
journal, January 2011
- Polfer, Nick C.
- Chemical Society Reviews, Vol. 40, Issue 5
Differentiation of Isomers by Wavelength-Tunable Infrared Multiple-Photon Dissociation-Mass Spectrometry: Application to Glucose-Containing Disaccharides
journal, December 2005
- Polfer, Nick C.; Valle, Jose J.; Moore, David T.
- Analytical Chemistry, Vol. 78, Issue 3
Subcellular Peptide Localization in Single Identified Neurons by Capillary Microsampling Mass Spectrometry
journal, August 2018
- Zhang, Linwen; Khattar, Nikkita; Kemenes, Ildiko
- Scientific Reports, Vol. 8, Issue 1
Observed metabolic asymmetry within soybean root nodules reflects unexpected complexity in rhizobacteria-legume metabolite exchange
journal, June 2018
- Veličković, Dušan; Agtuca, Beverly J.; Stopka, Sylwia A.
- The ISME Journal, Vol. 12, Issue 9
Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli
journal, June 2009
- Bennett, Bryson D.; Kimball, Elizabeth H.; Gao, Melissa
- Nature Chemical Biology, Vol. 5, Issue 8
Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells
journal, July 2010
- Taniguchi, Y.; Choi, P. J.; Li, G. -W.
- Science, Vol. 329, Issue 5991
The Symbiosome: Legume and Rhizobia Co-evolution toward a Nitrogen-Fixing Organelle?
journal, January 2018
- Coba de la Peña, Teodoro; Fedorova, Elena; Pueyo, José J.
- Frontiers in Plant Science, Vol. 8
A Nodule-Specific Protein Secretory Pathway Required for Nitrogen-Fixing Symbiosis
journal, February 2010
- Wang, D.; Griffitts, J.; Starker, C.
- Science, Vol. 327, Issue 5969
Detecting bimodality in astronomical datasets
journal, December 1994
- Ashman, Keith A.; Bird, Christina M.; Zepf, Stephen E.
- The Astronomical Journal, Vol. 108
Metabolic Noise and Distinct Subpopulations Observed by Single Cell LAESI Mass Spectrometry of Plant Cells in situ
journal, November 2018
- Stopka, Sylwia A.; Khattar, Rikkita; Agtuca, Beverly J.
- Frontiers in Plant Science, Vol. 9
Transcriptional Reprogramming of Legume Genomes: Perspective and Challenges Associated With Single-Cell and Single Cell-Type Approaches During Nodule Development
journal, November 2018
- Libault, Marc
- Frontiers in Plant Science, Vol. 9
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
journal, January 2008
- DeBerardinis, Ralph J.; Lum, Julian J.; Hatzivassiliou, Georgia
- Cell Metabolism, Vol. 7, Issue 1
13C-flux Analysis Reveals NADPH-balancing Transhydrogenation Cycles in Stationary Phase of Nitrogen-starving Bacillus subtilis
journal, August 2012
- Rühl, Martin; Le Coq, Dominique; Aymerich, Stéphane
- Journal of Biological Chemistry, Vol. 287, Issue 33
Metabolic Reconstruction and Modeling of Nitrogen Fixation in Rhizobium etli
journal, January 2007
- Resendis-Antonio, Osbaldo; Reed, Jennifer L.; Encarnación, Sergio
- PLoS Computational Biology, Vol. 3, Issue 10