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Nat Methods. 2014 Apr;11(4):417-22. doi: 10.1038/nmeth.2869. Epub 2014 Mar 2.

Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry.

Author information

1
1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2].
2
1] Department of Chemistry, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland. [2] Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland. [3].
3
1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2] Systems Biology Ph.D. Program, Life Science Zürich Graduate School, ETH Zürich and University of Zürich, Zürich, Switzerland.
4
1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2] Molecular Life Science Ph.D. Program, Life Science Zürich Graduate School, ETH Zürich and University of Zürich, Zürich, Switzerland.
5
Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
6
Department of Chemistry, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
7
Department of Computer Science, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
8
Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland.
9
Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.

Abstract

Mass cytometry enables high-dimensional, single-cell analysis of cell type and state. In mass cytometry, rare earth metals are used as reporters on antibodies. Analysis of metal abundances using the mass cytometer allows determination of marker expression in individual cells. Mass cytometry has previously been applied only to cell suspensions. To gain spatial information, we have coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution; with the availability of additional isotopes, measurement of over 100 markers will be possible. We applied imaging mass cytometry to human breast cancer samples, allowing delineation of cell subpopulations and cell-cell interactions and highlighting tumor heterogeneity. Imaging mass cytometry complements existing imaging approaches. It will enable basic studies of tissue heterogeneity and function and support the transition of medicine toward individualized molecularly targeted diagnosis and therapies.

Comment in

PMID:
24584193
DOI:
10.1038/nmeth.2869
[Indexed for MEDLINE]

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