Advertisement

Single-Cell Metabolomics by Mass Spectrometry

  • Bindesh ShresthaEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2064)

Abstract

Single-cell level metabolomics gives a snapshot of small molecules, intermediates, and products of cellular metabolism within a biological system. These small molecules, typically less than 1 kDa in molecular weight, often provide the basis of biochemical heterogeneity within cells. The molecular differences between cells with a cell type are often attributed to random stochastic biochemical processes, cell cycle stages, environmental stress, and diseased states. In this chapter, current limitations and challenges in single-cell analysis by mass spectrometry will be discussed alongside the prospects of single-cell metabolomics in systems biology. A few selected example of the recent development in mass spectrometry tools to unravel single-cell metabolomics will be described as well.

Key words

Single-cell analysis Single cell Single-cell mass spectrometry Single-cell metabolomics Single-cell metabolites 

References

  1. 1.
    Macaulay IC, Ponting CP, Voet T (2017) Single-cell multiomics: multiple measurements from single cells. Trends Genet 33(2):155–168CrossRefGoogle Scholar
  2. 2.
    Zheng XT, Li CM (2012) Single cell analysis at the nanoscale. Chem Soc Rev 41(6):2061–2071CrossRefGoogle Scholar
  3. 3.
    Galler K, Bräutigam K, Große C, Popp JR, Neugebauer U (2014) Making a big thing of a small cell ? Recent advances in single cell analysis. Analyst 139(6):1237–1273CrossRefGoogle Scholar
  4. 4.
    Miller A, Nagy C, Knapp B, Laengle J, Ponweiser E, Groeger M, Starkl P, Bergmann M, Wagner O, Haschemi A (2017) Exploring metabolic configurations of single cells within complex tissue microenvironments. Cell Metab 26(5):788–800.e6CrossRefGoogle Scholar
  5. 5.
    Fujii T, Matsuda S, Tejedor ML, Esaki T, Sakane I, Mizuno H, Tsuyama N, Masujima T (2015) Direct metabolomics for plant cells by live single-cell mass spectrometry. Nat Protoc 10(9):1445CrossRefGoogle Scholar
  6. 6.
    Shrestha B, Vertes A (2009) In situ metabolic profiling of single cells by laser ablation electrospray ionization mass spectrometry. Anal Chem 81(20):8265–8271CrossRefGoogle Scholar
  7. 7.
    Zhang L, Foreman DP, Grant PA, Shrestha B, Moody SA, Villiers F, Kwak JM, Vertes A (2014) In situ metabolic analysis of single plant cells by capillary microsampling and electrospray ionization mass spectrometry with ion mobility separation. Analyst 139(20):5079–5085CrossRefGoogle Scholar
  8. 8.
    Heath JR, Ribas A, Mischel PS (2016) Single-cell analysis tools for drug discovery and development. Nat Rev Drug Discov 15(3):204CrossRefGoogle Scholar
  9. 9.
    Trouillon R, Passarelli MK, Wang J, Kurczy ME, Ewing AG (2013) Chemical analysis of single cells. Anal Chem 85(2):522–542CrossRefGoogle Scholar
  10. 10.
    Zenobi R (2013) Single-cell metabolomics: analytical and biological perspectives. Science 342(6163):1243259CrossRefGoogle Scholar
  11. 11.
    Zhang L, Vertes A (2018) Single-cell mass spectrometry approaches to explore cellular heterogeneity. Angew Chem Int Ed 57(17):4466–4477CrossRefGoogle Scholar
  12. 12.
    Wang D, Bodovitz S (2010) Single cell analysis: the new frontier in ‘omics’. Trends Biotechnol 28(6):281–290CrossRefGoogle Scholar
  13. 13.
    Yao Y, Liu R, Shin MS, Trentalange M, Allore H, Nassar A, Kang I, Pober JS, Montgomery RR (2014) CyTOF supports efficient detection of immune cell subsets from small samples. J Immunol Methods 415:1–5CrossRefGoogle Scholar
  14. 14.
    Bandura DR, Baranov VI, Ornatsky OI, Antonov A, Kinach R, Lou X, Pavlov S, Vorobiev S, Dick JE, Tanner SD (2009) Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem 81(16):6813–6822CrossRefGoogle Scholar
  15. 15.
    Cahill JF, Kertesz V, Van Berkel GJ (2016) Laser dissection sampling modes for direct mass spectral analysis. Rapid Commun Mass Spectrom 30(5):611–619CrossRefGoogle Scholar
  16. 16.
    Mao S, Li W, Zhang Q, Zhang W, Huang Q, Lin J-M (2018) Cell analysis on chip-mass spectrometry. TrAC Trend Anal Chem 107:43–59CrossRefGoogle Scholar
  17. 17.
    Li L, Garden RW, Sweedler JV (2000) Single-cell MALDI: a new tool for direct peptide profiling. Trends Biotechnol 18(4):151–160CrossRefGoogle Scholar
  18. 18.
    Bhattacharya SH, Gal AA, Murray KK (2003) Laser capture microdissection MALDI for direct analysis of archival tissue. J Proteome Res 2(1):95–98CrossRefGoogle Scholar
  19. 19.
    Walker BN, Stolee JA, Vertes A (2012) Nanophotonic ionization for ultratrace and single-cell analysis by mass spectrometry. Anal Chem 84(18):7756–7762CrossRefGoogle Scholar
  20. 20.
    Northen TR, Yanes O, Northen MT, Marrinucci D, Uritboonthai W, Apon J, Golledge SL, Nordstrom A, Siuzdak G (2007) Clathrate nanostructures for mass spectrometry. Nature 449(7165):1033–1036CrossRefGoogle Scholar
  21. 21.
    Shrestha B, Sripadi P, Reschke BR, Henderson HD, Powell MJ, Moody SA, Vertes A (2014) Subcellular metabolite and lipid analysis of Xenopus laevis eggs by LAESI mass spectrometry. PLoS One 9(12):e115173CrossRefGoogle Scholar
  22. 22.
    Mizuno H, Tsuyama N, Harada T, Masujima T (2008) Live single-cell video-mass spectrometry for cellular and subcellular molecular detection and cell classification. J Mass Spectrom 43(12):1692–1700CrossRefGoogle Scholar
  23. 23.
    Tsuyama N, Mizuno H, Tokunaga E, Masujima T (2008) Live single-cell molecular analysis by video-mass spectrometry. Anal Sci 24(5):559–561CrossRefGoogle Scholar
  24. 24.
    Gong X, Zhao Y, Cai S, Fu S, Yang C, Zhang S, Zhang X (2014) Single cell analysis with probe ESI-mass spectrometry: detection of metabolites at cellular and subcellular levels. Anal Chem 86(8):3809–3816CrossRefGoogle Scholar
  25. 25.
    Zhang L, Vertes A (2015) Energy charge, redox state, and metabolite turnover in single human hepatocytes revealed by capillary microsampling mass spectrometry. Anal Chem 87(20):10397–10405CrossRefGoogle Scholar
  26. 26.
    Stopka SA, Agtuca BJ, Koppenaal DW, Paša-Tolić L, Stacey G, Vertes A, Anderton CR (2017) Laser-ablation electrospray ionization mass spectrometry with ion mobility separation reveals metabolites in the symbiotic interactions of soybean roots and rhizobia. Plant J 91(2):340–354CrossRefGoogle Scholar
  27. 27.
    Zhang X, Quinn K, Cruickshank-Quinn C, Reisdorph R, Reisdorph N (2018) The application of ion mobility mass spectrometry to metabolomics. Curr Opin Chem Biol 42:60–66CrossRefGoogle Scholar
  28. 28.
    Paglia G, Williams JP, Menikarachchi L, Thompson JW, Tyldesley-Worster R, Halldórsson S d, Rolfsson O, Moseley A, Grant D, Langridge J (2014) Ion mobility derived collision cross sections to support metabolomics applications. Anal Chem 86(8):3985–3993CrossRefGoogle Scholar
  29. 29.
    Zhou Z, Tu J, Zhu Z-J (2018) Advancing the large-scale CCS database for metabolomics and lipidomics at the machine-learning era. Curr Opin Chem Biol 42:34–41CrossRefGoogle Scholar
  30. 30.
    Onjiko RM, Portero EP, Moody SA, Nemes P (2017) In situ microprobe single-cell capillary electrophoresis mass spectrometry: metabolic reorganization in single differentiating cells in the live vertebrate (Xenopus laevis) embryo. Anal Chem 89(13):7069–7076CrossRefGoogle Scholar
  31. 31.
    Portero EP, Nemes P (2019) Dual cationic–anionic profiling of metabolites in a single identified cell in a live Xenopus laevis embryo by microprobe CE-ESI-MS. Analyst 144(3):892–900CrossRefGoogle Scholar
  32. 32.
    Budnik B, Levy E, Harmange G, Slavov N (2018) SCoPE-MS: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation. Genome Biol 19(1):161CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Waters CorporationMilfordUSA

Personalised recommendations