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High-throughput chromatin accessibility profiling at single-cell resolution

Author

Listed:
  • Anja Mezger

    (Stanford University
    Karolinska Institute)

  • Sandy Klemm

    (Stanford University)

  • Ishminder Mann

    (Takara Bio USA)

  • Kara Brower

    (Stanford University)

  • Alain Mir

    (Takara Bio USA)

  • Magnolia Bostick

    (Takara Bio USA)

  • Andrew Farmer

    (Takara Bio USA)

  • Polly Fordyce

    (Stanford University
    Stanford University
    Stanford University
    Chan Zuckerberg Biohub)

  • Sten Linnarsson

    (Karolinska Institute)

  • William Greenleaf

    (Stanford University
    Chan Zuckerberg Biohub
    Stanford University)

Abstract

Here we develop a high-throughput single-cell ATAC-seq (assay for transposition of accessible chromatin) method to measure physical access to DNA in whole cells. Our approach integrates fluorescence imaging and addressable reagent deposition across a massively parallel (5184) nano-well array, yielding a nearly 20-fold improvement in throughput (up to ~1800 cells/chip, 4–5 h on-chip processing time) and library preparation cost (~81¢ per cell) compared to prior microfluidic implementations. We apply this method to measure regulatory variation in peripheral blood mononuclear cells (PBMCs) and show robust, de novo clustering of single cells by hematopoietic cell type.

Suggested Citation

  • Anja Mezger & Sandy Klemm & Ishminder Mann & Kara Brower & Alain Mir & Magnolia Bostick & Andrew Farmer & Polly Fordyce & Sten Linnarsson & William Greenleaf, 2018. "High-throughput chromatin accessibility profiling at single-cell resolution," Nature Communications, Nature, vol. 9(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05887-x
    DOI: 10.1038/s41467-018-05887-x
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