A rapid and robust method for single cell chromatin accessibility profiling

被引：160

作者：

Chen, Xi ^{[1
]}

Miragaia, Ricardo J. ^{[1
,4
]}

Natarajan, Kedar Nath ^{[1
,5
]}

Teichmann, Sarah A. ^{[1
,2
,3
]}

机构：

[1] Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England

[2] EMBL European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England

[3] Cavendish Lab, Theory Condensed Matter, 19 JJ Thomson Ave, Cambridge CB3 0HE, England

[4] MedImmune, Sir Aaron Klug Bldg,Granta Pk, Cambridge CB21 6GH, England

[5] Univ So Denmark, Funct Biol & Metab Unit, Biochem & Mol Biol, DK-5230 Odense, Denmark

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

英国惠康基金; 欧洲研究理事会;

关键词：

T-BET; TRANSPOSITION; MEMORY; TRANSCRIPTION;

D O I：

10.1038/s41467-018-07771-0

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The assay for transposase-accessible chromatin using sequencing (ATAC-seq) is widely used to identify regulatory regions throughout the genome. However, very few studies have been performed at the single cell level (scATAC-seq) due to technical challenges. Here we developed a simple and robust plate-based scATAC-seq method, combining upfront bulk Tn5 tagging with single-nuclei sorting. We demonstrate that our method works robustly across various systems, including fresh and cryopreserved cells from primary tissues. By profiling over 3000 splenocytes, we identify distinct immune cell types and reveal cell type-specific regulatory regions and related transcription factors.

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