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Multiparameter Flow Cytometry: Advances in High Resolution Analysis

  • O'Donnell, Erika A. (Research and Development, BD Biosciences) ;
  • Ernst, David N. (Research and Development, BD Biosciences) ;
  • Hingorani, Ravi (Research and Development, BD Biosciences)
  • Received : 2013.02.15
  • Accepted : 2013.02.25
  • Published : 2013.04.30

Abstract

Over the past 40 years, flow cytometry has emerged as a leading, application-rich technology that supports high-resolution characterization of individual cells which function in complex cellular networks such as the immune system. This brief overview highlights advances in multiparameter flow cytometric technologies and reagent applications for characterization and functional analysis of cells modulating the immune network. These advances significantly support highthroughput and high-content analyses and enable an integrated understanding of the cellular and molecular interactions that underlie complex biological systems.

Keywords

References

  1. Shapiro, H. M. 2003. Practical flow cytometry. 4th ed. Wiley-Liss, Hoboken, NJ.
  2. Henel, G and J. L. Schmitz. 2007. Basic theory and clinical applications of flow cytometry. Lab. Med. 38: 428-436. https://doi.org/10.1309/GHLEWLV0CD8025JL
  3. Hayashi, T., N. Shibata, R. Okumura, T. Kudome, O. Nishimura, H. Tarui, and K. Agata. 2010. Single-cell gene profiling of planarian stem cells using fluorescent activated cell sorting and its "index sorting" function for stem cell research. Dev. Growth. Differ. 52: 131-144. https://doi.org/10.1111/j.1440-169X.2009.01157.x
  4. Doležel, J., J. Vrána, J. Safar, J. Bartos, M. Kubalakova, and H. Simkova. 2012. Chromosomes in the flow to simplify genome analysis. Funct. Integr. Genomics 12: 397-416. https://doi.org/10.1007/s10142-012-0293-0
  5. Tighe, P., O. Negm, I. Todd, and L. Fairclough. 2013. Utility, reliability and reproducibility of immunoassay multiplex kits. Methods [Epub ahead of print].
  6. Ernst, D., G. Bolton, D. Recktenwald, M. J. Cameron, A. Danesh, D. Persad, D. J. Kelvin, and A. Gaur. 2006. Bead-based flow cytometric assays: A multiplex assay platform with applications in diagnostic microbiology. In Advanced techniques in diagnostic microbiology. Y.-W. Tang and C. W. Stratton, eds. Springer, New York, U.S.A. p.427-443.
  7. Morgan, E., R. Varro, H. Sepulveda, J. A. Ember, J. Apgar, J. Wilson, L. Lowe, R. Chen, L. Shivraj, A. Agadir, R. Campos, D. Ernst, and A. Gaur. 2004. Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. Clin. Immunol. 110: 252-266. https://doi.org/10.1016/j.clim.2003.11.017
  8. Funato, Y., H. Baumhover, D. Grantham-Wright, J. Wilson, D. Ernst, and H. Sepulveda. 2002. Simultaneous measurement of six human cytokines using the Cytometric Bead Array System, a multiparameter immunoassay system for flow cytometry. Cytometry Res. 12: 93-97.
  9. Cook, E. B., J. L. Stahl, L. Lowe, R. Chen, E. Morgan, J. Wilson, R. Varro, A. Chan, F. M. Graziano, and N. P. Barney. 2001. Simultaneous measurement of six cytokines in a single sample of human tears using microparticle-based flow cytometry: allergics vs. non-allergics. J. Immunol. Methods 254: 109-118. https://doi.org/10.1016/S0022-1759(01)00407-0
  10. Chattopadhyay, P. K. and M. Roederer. 2012. Cytometry: today's technology and tomorrow's horizons. Methods 57: 251-258. https://doi.org/10.1016/j.ymeth.2012.02.009
  11. Herzenberg, L. A., D. Parks, B. Sahaf, O. Perez, M. Roederer, and L. A. Herzenberg. 2002. The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. Clin. Chem. 48: 1819-1827.
  12. Zhang, P., N. Zhao, Z. Zeng, C. C. Chang, and Y. Zu. 2010. Combination of an aptamer probe to CD4 and antibodies for multicolored cell phenotyping. Am. J. Clin. Pathol. 134: 586-593. https://doi.org/10.1309/AJCP55KQYWSGZRKC
  13. Telford, W. G., T. Hawley, F. Subach, V. Verkhusha, and R. G. Hawley. 2012. Flow cytometry of fluorescent proteins. Methods 57: 318-330. https://doi.org/10.1016/j.ymeth.2012.01.003
  14. Robinson, J. P., B. Rajwa, V. Patsekin, and V. J. Davisson. 2012. Computational analysis of high-throughput flow cytometry data. Expert. Opin. Drug Discov. 7: 679-693. https://doi.org/10.1517/17460441.2012.693475
  15. De Rosa, S. C., J. M. Brenchley, and M. Roederer. 2003. Beyond six colors: a new era in flow cytometry. Nat. Med. 9: 112-117. https://doi.org/10.1038/nm0103-112
  16. Appay, V., R. A. van Lier, F. Sallusto, and M. Roederer. 2008. Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A 73: 975-983.
  17. Craig, F. E. and K. A. Foon. 2008. Flow cytometric immunophenotyping for hematologic neoplasms. Blood 111: 3941-3967. https://doi.org/10.1182/blood-2007-11-120535
  18. Danna, E. A. and G. P. Nolan. 2006. Transcending the biomarker mindset: deciphering disease mechanisms at the single cell level. Curr. Opin. Chem. Biol. 10: 20-27. https://doi.org/10.1016/j.cbpa.2005.12.021
  19. Krutzik, P. O., J. M. Crane, M. R. Clutter, and G. P. Nolan. 2008. High-content single-cell drug screening with phosphospecific flow cytometry. Nat. Chem. Biol. 4: 132-142. https://doi.org/10.1038/nchembio.2007.59
  20. Maino, V. C. and L. J. Picker. 1998. Identification of functional subsets by flow cytometry: intracellular detection of cytokine expression. Cytometry 34: 207-215. https://doi.org/10.1002/(SICI)1097-0320(19981015)34:5<207::AID-CYTO1>3.0.CO;2-J
  21. Perez, O. D., D. Mitchell, R. Campos, G. J. Gao, L. Li, and G. P. Nolan. 2005. Multiparameter analysis of intracellular phosphoepitopes in immunophenotyped cell populations by flow cytometry. Curr. Protoc. Cytom. Chapter 6: Unit 6.20.
  22. Chattopadhyay, P. K., B. Gaylord, A. Palmer, N. Jiang, M. A. Raven, G. Lewis, M. A. Reuter, A. K. Nur-ur Rahman, D. A. Price, M. R. Betts, and M. Roederer. 2012 Brilliant violet fluorophores: a new class of ultrabright fluorescent compounds for immunofluorescence experiments. Cytometry A 81: 456-466.
  23. Chattopadhyay, P. K. 2011. Quantum dot technology in flow cytometry. Methods Cell Biol. 102: 463-477. https://doi.org/10.1016/B978-0-12-374912-3.00018-3
  24. Kalina, T., J. Flores-Montero, V. H. van der Velden, M. Martin-Ayuso, S. Böttcher, M. Ritgen, J. Almeida, L. Lhermitte, V. Asnafi, A. Mendonça, R. de Tute, M. Cullen, L. Sedek, M. B. Vidriales, J. J. Perez, J. G. te Marvelde, E. Mejstrikova, O. Hrusak, T. Szczepański, J. J. van Dongen, and A. Orfao; EuroFlow Consortium (EU-FP6, LSHB-CT-2006- 018708). 2012. EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols. Leukemia 26: 1986-2010. https://doi.org/10.1038/leu.2012.122
  25. Crissman, H. A., Z. Darzynkiewicz, R. A. Tobey, and J. A. Steinkamp. 1985. Correlated measurements of DNA, RNA, and protein in individual cells by flow cytometry. Science 228: 1321-1324. https://doi.org/10.1126/science.2408339
  26. Peixoto, A., M. Monteiro, B. Rocha, and H. Veiga-Fernandes. 2004. Quantification of multiple gene expression in individual cells. Genome Res. 14: 1938-1947. https://doi.org/10.1101/gr.2890204
  27. Krutzik, P. O., M. R. Clutter, A. Trejo, and G. P. Nolan. 2011. Fluorescent cell barcoding for multiplex flow cytometry. Curr. Protoc. Cytom. Chapter 6: Unit 6.31.
  28. Krutzik, P. O. and G. P. Nolan. 2006. Fluorescent cell barcoding in flow cytometry allows high-throughput drug screening and signaling profiling. Nat. Methods 3: 361-368. https://doi.org/10.1038/nmeth872
  29. Bodenmiller, B., E. R. Zunder, R. Finck, T. J. Chen, E. S. Savig, R. V. Bruggner, E. F. Simonds, S. C. Bendall, K. Sachs, P. O. Krutzik, and G. P. Nolan. 2012. Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators. Nat. Biotechnol. 30: 858-867. https://doi.org/10.1038/nbt.2317
  30. Nomura, L., V. C. Maino, and H. T. Maecker. 2008. Standardization and optimization of multiparameter intracellular cytokine staining. Cytometry A 73: 984-991.
  31. Suni, M. A., H. S. Dunn, P. L. Orr, R. de Laat, E. Sinclair, S. A. Ghanekar, B. M. Bredt, J. F. Dunne, V. C. Maino, and H. T. Maecker. 2003. Performance of plate-based cytokine flow cytometry with automated data analysis. BMC Immunol. 4: 9. https://doi.org/10.1186/1471-2172-4-9
  32. Gray, J. W. and Z. Darzynkiewicz. 1987. Techniques in cell cycle analysis. Humana Press, Totowa, NJ.
  33. Darzynkiewicz, Z., F. Traganos, T. Sharpless, and M. R. Melamed. 1976. Lymphocyte stimulation: a rapid multiparameter analysis. Proc. Natl. Acad. Sci. U.S.A. 73: 2881-2884. https://doi.org/10.1073/pnas.73.8.2881
  34. Cappella, P., F. Gasparri, M. Pulici, and J. Moll. 2008. A novel method based on click chemistry, which overcomes limitations of cell cycle analysis by classical determination of BrdU incorporation, allowing multiplex antibody staining. Cytometry A 73: 626-636.
  35. Feig, C. and M. E. Peter. 2007. How apoptosis got the immune system in shape. Eur. J. Immunol. 37 Suppl 1: S61-70. https://doi.org/10.1002/eji.200737462
  36. Hanahan, D. and R. A. Weinberg. 2011. Hallmarks of cancer: the next generation. Cell 144: 646-674. https://doi.org/10.1016/j.cell.2011.02.013
  37. Wlodkowic, D., W. Telford, J. Skommer, and Z. Darzynkiewicz. 2011. Apoptosis and beyond: cytometry in studies of programmed cell death. Methods Cell Biol. 103: 55-98. https://doi.org/10.1042/BC20100111
  38. Wlodkowic, D., J. Skommer, and Z. Darzynkiewicz. 2010. Cytometry in cell necrobiology revisited. Recent advances and new vistas. Cytometry A 77: 591-606.
  39. Tanaka, T., H. D. Halicka, F. Traganos, K. Seiter, and Z. Darzynkiewicz. 2007. Induction of ATM activation, histone H2AX phosphorylation and apoptosis by etoposide: relation to cell cycle phase. Cell Cycle 6: 371-376. https://doi.org/10.4161/cc.6.3.3835
  40. Schulz, K. R., E. A. Danna, P. O. Krutzik, and G. P. Nolan. 2012. Single-cell phospho-protein analysis by flow cytometry. Curr. Protoc. Immunol. Chapter 8: Unit 8.17.1-20.
  41. Juan, G., F. Traganos, W. M. James, J. M. Ray, M. Roberge, D. M. Sauve, H. Anderson, and Z. Darzynkiewicz. 1998. Histone H3 phosphorylation and expression of cyclins A and B1 measured in individual cells during their progression through G2 and mitosis. Cytometry 32: 71-77. https://doi.org/10.1002/(SICI)1097-0320(19980601)32:2<71::AID-CYTO1>3.0.CO;2-H
  42. Fleisher, T. A., S. E. Dorman, J. A. Anderson, M. Vail, M. R. Brown, and S. M. Holland. 1999. Detection of intracellular phosphorylated STAT-1 by flow cytometry. Clin. Immunol. 90: 425-430. https://doi.org/10.1006/clim.1998.4654
  43. Chow, S., H. Patel, and D. W. Hedley. 2001. Measurement of MAP kinase activation by flow cytometry using phospho- specific antibodies to MEK and ERK: potential for pharmacodynamic monitoring of signal transduction inhibitors. Cytometry 46: 72-78. https://doi.org/10.1002/cyto.1067
  44. Zell, T., A. Khoruts, E. Ingulli, J. L. Bonnevier, D. L. Mueller, and M. K. Jenkins. 2001. Single-cell analysis of signal transduction in CD4 T cells stimulated by antigen in vivo. Proc. Natl. Acad. Sci. U.S.A. 98: 10805-10810. https://doi.org/10.1073/pnas.191567898
  45. Perez, O. D. and G. P. Nolan. 2002. Simultaneous measurement of multiple active kinase states using polychromatic flow cytometry. Nat. Biotechnol. 20: 155-162. https://doi.org/10.1038/nbt0202-155
  46. Tazzari, P. L., A. Cappellini, R. Bortul, F. Ricci, A. M. Billi, G. Tabellini, R. Conte, and A. M. Martelli. 2002. Flow cytometric detection of total and serine 473 phosphorylated Akt. J. Cell. Biochem. 86: 704-715. https://doi.org/10.1002/jcb.10262
  47. Krutzik, P. O. and G. P. Nolan. 2003. Intracellular phospho- protein staining techniques for flow cytometry: monitoring single cell signaling events. Cytometry A 55: 61-70.
  48. Chow, S., D. Hedley, P. Grom, R. Magari, J. W. Jacobberger, and T. V. Shankey. 2005. Whole blood fixation and permeabilization protocol with red blood cell lysis for flow cytometry of intracellular phosphorylated epitopes in leukocyte subpopulations. Cytometry A 67: 4-17.
  49. Suni, M. A. and V. C. Maino. 2011. Flow cytometric analysis of cell signaling proteins. Methods Mol. Biol. 717: 155-169. https://doi.org/10.1007/978-1-61779-024-9_9
  50. Irish, J. M., D. K. Czerwinski, G. P. Nolan, and R. Levy. 2006. Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells. Blood 108: 3135-3142. https://doi.org/10.1182/blood-2006-02-003921
  51. Sadeghi, K., A. Berger, M. Langgartner, A. R. Prusa, M. Hayde, K. Herkner, A. Pollak, A. Spittler, and E. Forster- Waldl. 2007. Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. J. Infect. Dis. 195: 296-302. https://doi.org/10.1086/509892
  52. Zeiser, R., D. B. Leveson-Gower, E. A. Zambricki, N. Kambham, A. Beilhack, J. Loh, J. Z. Hou, and R. S. Negrin. 2008. Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells. Blood 111: 453-462. https://doi.org/10.1182/blood-2007-06-094482
  53. Perfetto, S. P., P. K. Chattopadhyay, L. Lamoreaux, R. Nguyen, D. Ambrozak, R. A. Koup, and M. Roederer. 2010. Amine-reactive dyes for dead cell discrimination in fixed samples. Curr. Protoc. Cytom. Chapter 9: Unit 9.34.
  54. Henriksen, M., B. Miller, J. Newmark, Y. Al-Kofahi, and E. Holden. 2011. Laser scanning cytometry and its applications: a pioneering technology in the field of quantitative imaging cytometry. Methods Cell Biol. 102: 161-205.
  55. Zuba-Surma, E. K. and M. Z. Ratajczak. 2011. Analytical capabilities of the ImageStream cytometer. Methods Cell Biol. 102: 207-230. https://doi.org/10.1016/B978-0-12-374912-3.00008-0
  56. Clutter, M. R., G. C. Heffner, P. O. Krutzik, K. L. Sachen, and G. P. Nolan. 2010. Tyramide signal amplification for analysis of kinase activity by intracellular flow cytometry. Cytometry A 77: 1020-1031.
  57. Krutzik, P. O., A. Trejo, K. R. Schulz, and G. P. Nolan. 2011. Phospho flow cytometry methods for the analysis of kinase signaling in cell lines and primary human blood samples. Methods Mol. Biol. 699: 179-202. https://doi.org/10.1007/978-1-61737-950-5_9
  58. Kuckuck, F. W., B. S. Edwards, and L. A. Sklar. 2001. High throughput flow cytometry. Cytometry 44: 83-90. https://doi.org/10.1002/1097-0320(20010501)44:1<83::AID-CYTO1085>3.0.CO;2-O
  59. Bashashati, A. and R. R. Brinkman. 2009. A survey of flow cytometry data analysis methods. Adv. Bioinformatics 584603.
  60. Lugli, E., M. Roederer, and A. Cossarizza. 2010. Data analysis in flow cytometry: the future just started. Cytometry A 77: 705-713.
  61. Aghaeepour, N., R. Nikolic, H. H. Hoos, and R. R. Brinkman. 2011. Rapid cell population identification in flow cytometry data. Cytometry A 79: 6-13.
  62. Sachs, K., A. J. Gentles, R. Youland, S. Itani, J. Irish, G. P. Nolan, and S. K. Plevritis. 2009. Characterization of patient specific signaling via augmentation of Bayesian networks with disease and patient state nodes. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009: 6624-6627.
  63. Qiu, P., E. F. Simonds, S. C. Bendall, K. D. Gibbs Jr, R. V. Bruggner, M. D. Linderman, K. Sachs, G. P. Nolan, and S. K. Plevritis. 2011. Extracting a cellular hierarchy from high-dimensional cytometry data with SPADE. Nat. Biotechnol. 29: 886-891. https://doi.org/10.1038/nbt.1991
  64. Pedreira, C. E., E. S. Costa, S. Barrena, Q. Lecrevisse, J. Almeida, J. J. van Dongen, and A. Orfao; EuroFlow Consortium. 2008. Generation of flow cytometry data files with a potentially infinite number of dimensions. Cytometry A 73: 834-846.
  65. Bagwell, C. B. 2011. Breaking the dimensionality barrier. Methods Mol. Biol. 699: 31-51. https://doi.org/10.1007/978-1-61737-950-5_2
  66. Bendall, S. C., E. F. Simonds, P. Qiu, A. D. Amir el, P. O. Krutzik, R. Finck, R. V. Bruggner, R. Melamed, A. Trejo, O. I. Ornatsky, R. S. Balderas, S. K. Plevritis, K. Sachs, D. Pe'er, S. D. Tanner, and G. P. Nolan. 2011. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332: 687-696. https://doi.org/10.1126/science.1198704
  67. Ornatsky, O., D. Bandura, V. Baranov, M. Nitz, M. A. Winnik, and S. Tanner. 2010. Highly multiparametric analysis by mass cytometry. J. Immunol. Methods 361: 1-20. https://doi.org/10.1016/j.jim.2010.07.002
  68. Auksorius, E., Y. Bromberg, R. Motiejúnaité, A. Pieretti, L. Liu, E. Coron, J. Aranda, A. M. Goldstein, B. E. Bouma, A. Kazlauskas, and G. J. Tearney. 2012. Dual-modality fluorescence and full-field optical coherence microscopy for biomedical imaging applications. Biomed. Opt. Express 3: 661-666 https://doi.org/10.1364/BOE.3.000661
  69. Barteneva, N. S., E. Fasler-Kan, and I. A. Vorobjev. 2012. Imaging flow cytometry: coping with heterogeneity in biological systems. J. Histochem. Cytochem. 60: 723-733. https://doi.org/10.1369/0022155412453052
  70. Pierzchalski, A., A. Mittag, and A. Tárnok. 2011. Introduction A: recent advances in cytometry instrumentation, probes, and methods--review. Methods Cell Biol. 102: 1-21. https://doi.org/10.1016/B978-0-12-374912-3.00001-8
  71. Shapiro, H. M. and N. G. Perlmutter. 2006. Personal cytometers: slow flow or no flow? Cytometry A 69: 620-630.
  72. Petersen, T. W., C. Brent Harrison, D. N. Horner, and G. van den Engh. 2012. Flow cytometric characterization of marine microbes. Methods 57: 350-358. https://doi.org/10.1016/j.ymeth.2012.07.001
  73. Wlodkowic, D., K. Khoshmanesh, J. Akagi, D. E. Williams, and J. M. Cooper. 2011. Wormometry-on-a-chip: Innovative technologies for in situ analysis of small multicellular organisms. Cytometry A 79: 799-813.
  74. Orozco, A. F. and D. E. Lewis. 2010. Flow cytometric analysis of circulating microparticles in plasma. Cytometry A 77: 502-514.
  75. Chang, Q. and D. Hedley. 2012. Emerging applications of flow cytometry in solid tumor biology. Methods 57: 359-367. https://doi.org/10.1016/j.ymeth.2012.03.027
  76. Tárnok, A., H. Ulrich, and J. Bocsi. 2010. Phenotypes of stem cells from diverse origin. Cytometry A 77: 6-10.
  77. Ochatt, S. J. 2008. Flow cytometry in plant breeding. Cytometry A 73: 581-598.
  78. Petrunkina, A. M. and R. A. Harrison. 2011. Cytometric solutions in veterinary andrology: Developments, advantages, and limitations. Cytometry A 79: 338-348.
  79. Müller, S. and G. Nebe-von-Caron. 2010. Functional single- cell analyses: flow cytometry and cell sorting of microbial populations and communities. FEMS Microbiol. Rev. 34: 554-587 https://doi.org/10.1111/j.1574-6976.2010.00214.x

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