PT - JOURNAL ARTICLE AU - Mezger, Anja AU - Klemm, Sandy AU - Mann, Ishminder AU - Brower, Kara AU - Mir, Alain AU - Bostick, Magnolia AU - Farmer, Andrew AU - Fordyce, Polly AU - Linnarsson, Sten AU - Greenleaf, William TI - High-throughput chromatin accessibility profiling at single-cell resolution AID - 10.1101/310284 DP - 2018 Jan 01 TA - bioRxiv PG - 310284 4099 - http://biorxiv.org/content/early/2018/04/28/310284.short 4100 - http://biorxiv.org/content/early/2018/04/28/310284.full AB - We have developed 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 hour on-chip processing time) and cost (~98ยข per cell) compared to prior microfluidic implementations. We applied 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.