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Ultra-sensitive digital quantification of proteins and mRNA in single cells

Author

Listed:
  • Jing Lin

    (University of Chicago
    University of Chicago)

  • Christian Jordi

    (University of Chicago
    University of Chicago
    ETH Zürich)

  • Minjun Son

    (University of Chicago
    University of Chicago)

  • Hoang Phan

    (University of Chicago
    University of Chicago)

  • Nir Drayman

    (University of Chicago
    University of Chicago)

  • Mustafa Fatih Abasiyanik

    (University of Chicago
    University of Chicago)

  • Luke Vistain

    (University of Chicago
    University of Chicago)

  • Hsiung-Lin Tu

    (University of Chicago
    University of Chicago
    Academia Sinica)

  • Savaş Tay

    (University of Chicago
    University of Chicago)

Abstract

Simultaneous measurement of proteins and mRNA in single cells enables quantitative understanding and modeling of cellular functions. Here, we present an automated microfluidic system for multi-parameter and ultra-sensitive protein/mRNA measurements in single cells. Our technology improves the sensitivity of digital proximity ligation assay by up to 55-fold, with a detection limit of 2277 proteins per cell and with detection efficiency of as few as 29 protein molecules. Our measurements using this system reveal higher mRNA/protein correlation in single mammalian cells than previous estimates. Furthermore, time-lapse imaging of herpes simplex virus 1 infected epithelial cells enabled by our device shows that expression of ICP4 -a major transcription factor regulating hundreds of viral genes- is only partially correlated with viral protein counts, suggesting that many cells go through abortive infection. These results highlight the importance of high-sensitivity protein/mRNA quantification for understanding fundamental molecular mechanisms in individual cells.

Suggested Citation

  • Jing Lin & Christian Jordi & Minjun Son & Hoang Phan & Nir Drayman & Mustafa Fatih Abasiyanik & Luke Vistain & Hsiung-Lin Tu & Savaş Tay, 2019. "Ultra-sensitive digital quantification of proteins and mRNA in single cells," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11531-z
    DOI: 10.1038/s41467-019-11531-z
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