High-throughput chromatin accessibility profiling at single-cell resolution

• DOI: 10.1038/s41467-018-05887-x
• Publication Date: 2018-09-03T14:30:41Z
• Authors: Anja Mezger; Sandy Klemm; Ishminder Mann; Kara Brower; Alain Mir; Magnolia Bostick; Andrew Farmer; Polly Fordyce; Sten Linnarsson; William Greenleaf
• Keywords: Single-Cell Analysis; Profiling (computer programming)

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