Abstract
We report an approach to barcode cells through cell-surface expression of programmable zinc-finger DNA-binding domains (surface zinc fingers, sZFs). We show that sZFs enable sequence-specific labeling of living cells by dsDNA, and we develop a sequential labeling approach to image more than three cell types in mixed populations using three fluorophores. We demonstrate the versatility of sZFs through applications in which they serve as surrogate reporters, function as selective cell capture reagents and facilitate targeted cellular delivery of viruses.
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Acknowledgements
This work was supported by US National Human Genome Research Institute grant P50 HG005550. SINmu plasmid for lentivirus experiments was a gift from P. Wang (University of Southern California).
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P.M. and G.M.C. conceived the study and designed the experiments. P.M. performed experiments. J.-H.L., D.L. and L.N. developed reagents. J.A. developed the image analysis suite and performed associated analyses. P.M., J.A. and G.M.C. wrote the manuscript with support from all authors.
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The authors declare no competing financial interests.
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Supplementary Figures 1–15, Supplementary Tables 1–4 and Supplementary Notes 1–3 (PDF 7215 kb)
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Mali, P., Aach, J., Lee, JH. et al. Barcoding cells using cell-surface programmable DNA-binding domains. Nat Methods 10, 403–406 (2013). https://doi.org/10.1038/nmeth.2407
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DOI: https://doi.org/10.1038/nmeth.2407
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