Single-cell analysis targeting the proteome

Abstract

The existence of cellular heterogeneity and its central relevance to biological phenomena provides a strong rationale for a need for analytical methods that enable analysis at the single-cell level. Analysis of the genome and transcriptome is possible at the single-cell level, but the comprehensive interrogation of the proteome with this level of resolution remains challenging. Single-cell protein analysis tools are advancing rapidly, however, and providing insights into collections of proteins with great relevance to cell and disease biology. Here, we review single-cell protein analysis technologies and assess their advantages and limitations. The emerging technologies presented have the potential to reveal new insights into tumour heterogeneity and therapeutic resistance, elucidate mechanisms of immune response and immunotherapy, and accelerate drug discovery.

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Fig. 1: Classification of single-cell protein analysis methods based on the location of target protein.
Fig. 2: Single-cell analysis of proteins using fluorescent probes.
Fig. 3: Antibody-based microfluidic approaches for single-cell protein analysis.
Fig. 4: Mass-spectrometry approaches for single-cell analysis of proteins.
Fig. 5: Multiplexed analysis of mRNAs and proteins in single cells.

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Acknowledgements

The authors thank the Canadian Institutes of Health Research (grant no. FDN-148415), the Natural Sciences and Engineering Research Council of Canada (grant no. 2016-06090), the Province of Ontario through the Ministry of Research, Innovation and Science (grant no. RE05-009) and the National Cancer Institute of the National Institutes of Health (grant no. 1R33CA204574). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the other funding agencies.

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Correspondence to Shana O. Kelley.

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Labib, M., Kelley, S.O. Single-cell analysis targeting the proteome. Nat Rev Chem 4, 143–158 (2020). https://doi.org/10.1038/s41570-020-0162-7

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