High-throughput chromatin accessibility profiling at single-cell resolution

被引：104

作者：

Mezger, Anja ^{[1
,2
]}

Klemm, Sandy ^{[1
]}

Mann, Ishminder ^{[3
]}

Brower, Kara ^{[4
]}

Mir, Alain ^{[3
]}

Bostick, Magnolia ^{[3
]}

Farmer, Andrew ^{[3
]}

Fordyce, Polly ^{[1
,4
,5
,6
]}

Linnarsson, Sten ^{[2
]}

Greenleaf, William ^{[1
,6
,7
]}

机构：

[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[2] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden

[3] Takara Bio USA, Mountain View, CA 94043 USA

[4] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[5] Stanford Univ, ChEM H Inst, Stanford, CA 94305 USA

[6] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

[7] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

瑞典研究理事会;

关键词：

B-CELLS; MACROPHAGES; LANDSCAPE; ALPHA;

D O I：

10.1038/s41467-018-05887-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 similar to 1800 cells/chip, 4-5 h on-chip processing time) and library preparation cost (similar to 81 cent 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.

引用

页数：6

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