From single cells to deep phenotypes in cancer

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In recent years, major advances in single-cell measurement systems have included the introduction of high-throughput versions of traditional flow cytometry that are now capable of measuring intracellular network activity, the emergence of isotope labels that can enable the tracking of a greater variety of cell markers and the development of super-resolution microscopy techniques that allow measurement of RNA expression in single living cells. These technologies will facilitate our capacity to catalog and bring order to the inherent diversity present in cancer cell populations. Alongside these developments, new computational approaches that mine deep data sets are facilitating the visualization of the shape of the data and enabling the extraction of meaningful outputs. These applications have the potential to reveal new insights into cancer biology at the intersections of stem cell function, tumor-initiating cells and multilineage tumor development. In the clinic, they may also prove important not only in the development of new diagnostic modalities but also in understanding how the emergence of tumor cell clones harboring different sets of mutations predispose patients to relapse or disease progression.

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Figure 1: Signaling-responsiveness–dependent heterogeneity can correlate with signaling outcomes26.
Figure 2: Most antibodies, either against surface proteins delineating immune cells or intracellular targets, can be adapted for use with the CyTOF instrument.


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G.P.N. is supported by the Rachford and Carlota A. Harris Endowed Professorship and grants from U19 AI057229, P01 CA034233, HHSN272200700038C, 1R01CA130826, CIRM DR1-01477 and RB2-01592, NCI RFA CA 09-011, NHLBI-HV-10-05(2), European Commission HEALTH.2010.1.2-1, and the Bill and Melinda Gates Foundation (GF12141-137101). S.C.B. is supported by the Damon Runyon Cancer Research Foundation Fellowship (DRG-2017-09). The authors would also like to thank M. Angelo for useful discussions pertaining to the information in Table 1.

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Correspondence to Garry P Nolan.

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G.P.N. is a paid consultant for, receives royalties from, or owns equity in the following companies whose products or services are directly or indirectly discussed in this article: Becton Dickinson, Nodality and DVS Sciences.

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Bendall, S., Nolan, G. From single cells to deep phenotypes in cancer. Nat Biotechnol 30, 639–647 (2012) doi:10.1038/nbt.2283

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