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Nat Commun. 2019 Jan 28;10(1):470. doi: 10.1038/s41467-018-08205-7.

Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity.

Liu L1,2,3, Liu C1,2,4, Quintero A5,6, Wu L1,2,4, Yuan Y1,2,4, Wang M1,2,4, Cheng M1,2,4, Leng L7,8, Xu L1,2, Dong G1,2, Li R1,2,3, Liu Y1,2,4, Wei X1,2,4, Xu J1,2,4, Chen X2, Lu H2, Chen D1,2, Wang Q1,2,4, Zhou Q1,2, Lin X1,2, Li G1,2, Liu S1,2, Wang Q5, Wang H9, Fink JL1, Gao Z10, Liu X1,2, Hou Y1,2, Zhu S1,2, Yang H1,11, Ye Y3, Lin G7,8,12, Chen F1,2,13, Herrmann C5,6, Eils R14,15, Shang Z16,17,18, Xu X19,20,21.

Author information

1
BGI-Shenzhen, Shenzhen, 518083, China.
2
China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.
3
Harbin Institute of Technology Shenzhen Graduate School, Xili University Town, Shenzhen, 518055, China.
4
BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China.
5
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
6
Health Data Science Unit, Heidelberg University Hospital, Heidelberg, 69120, Germany.
7
Institute of Reproductive & Stem Cell Engineering, Central South University, Changsha, 410078, China.
8
Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, 410078, China.
9
Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing, 100044, China.
10
Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200092, China.
11
James D. Watson Institute of Genome Sciences, Hangzhou, 310013, China.
12
National Engineering and Research Center of Human Stem Cell, Changsha, 410078, China.
13
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100, Copenhagen, Denmark.
14
Health Data Science Unit, Heidelberg University Hospital, Heidelberg, 69120, Germany. roland.eils@bihealth.de.
15
Center for Digital Health, Berlin Institute of Health and Charité, Berlin, 10117, Germany. roland.eils@bihealth.de.
16
BGI-Shenzhen, Shenzhen, 518083, China. shangzhouchun@genomics.cn.
17
China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China. shangzhouchun@genomics.cn.
18
Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200092, China. shangzhouchun@genomics.cn.
19
BGI-Shenzhen, Shenzhen, 518083, China. xuxun@genomics.cn.
20
China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China. xuxun@genomics.cn.
21
Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. xuxun@genomics.cn.

Abstract

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generate the first single cell integrated map of chromatin accessibility and transcriptome in early embryos and demonstrate the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states. The ability to obtain these two layers of omics data will help provide more accurate definitions of "single cell state" and enable the deconvolution of regulatory heterogeneity from complex cell populations.

PMID:
30692544
PMCID:
PMC6349937
DOI:
10.1038/s41467-018-08205-7
[Indexed for MEDLINE]
Free PMC Article

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