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High-throughput chromatin accessibility profiling at single-cell resolution

Anja Mezger, Sandy Klemm, Ishminder Mann, Kara Brower, Alain Mir, Magnolia Bostick, Andrew Farmer, Polly Fordyce, Sten Linnarsson and William Greenleaf ()
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Anja Mezger: Stanford University
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
Sten Linnarsson: Karolinska Institute
William Greenleaf: Stanford University

Nature Communications, 2018, vol. 9, issue 1, 1-6

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05887-x

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