Single-Cell DNA Methylome Sequencing and Bioinformatic Inference of Epigenomic Cell-State Dynamics

被引：314

作者：

Farlik, Matthias ^{[1
]}

Sheffield, Nathan C. ^{[1
]}

Nuzzo, Angelo ^{[1
]}

Datlinger, Paul ^{[1
]}

Schoenegger, Andreas ^{[1
]}

Klughammer, Johanna ^{[1
]}

Bock, Christoph ^{[1
,2
,3
]}

机构：

[1] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria

[2] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria

[3] Max Planck Inst Informat, D-66123 Saarbrucken, Germany

来源：

CELL REPORTS | 2015年 / 10卷 / 08期

关键词：

EMBRYONIC STEM-CELLS; PREIMPLANTATION EMBRYOS; METHYLATION; GENOME; DIFFERENTIATION; HETEROGENEITY; ARABIDOPSIS; RESOLUTION; BINDING; MAPS;

D O I：

10.1016/j.celrep.2015.02.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Methods for single-cell genome and transcriptome sequencing have contributed to our understanding of cellular heterogeneity, whereas methods for single-cell epigenomics are much less established. Here, we describe a whole-genome bisulfite sequencing (WGBS) assay that enables DNA methylation mapping in very small cell populations (mWGBS) and single cells (scWGBS). Our assay is optimized for profiling many samples at low coverage, and we describe a bioinformatic method that analyzes collections of single-cell methylomes to infer cell-state dynamics. Using these technological advances, we studied epigenomic cell-state dynamics in three in vitro models of cellular differentiation and pluripotency, where we observed characteristic patterns of epigenome remodeling and cell-to-cell heterogeneity. The described method enables single-cell analysis of DNA methylation in a broad range of biological systems, including embryonic development, stem cell differentiation, and cancer. It can also be used to establish composite methylomes that account for cell-to-cell heterogeneity in complex tissue samples.

引用

页码：1386 / 1397

页数：12

共 38 条

[31] Identifying and Characterizing Regulatory Sequences in the Human Genome with Chromatin Accessibility Assays [J].

Sheffield, Nathan C. ;

Furey, Terrence S. .

GENES, 2012, 3 (04) :651-670

[32] Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions [J].

Sheffield, Nathan C. ;

Thurman, Robert E. ;

Song, Lingyun ;

Safi, Alexias ;

Stamatoyannopoulos, John A. ;

Lenhard, Boris ;

Crawford, Gregory E. ;

Furey, Terrence S. .

GENOME RESEARCH, 2013, 23 (05) :777-788

[33]

Smallwood SA, 2014, NAT METHODS, V11, P817, DOI [10.1038/NMETH.3035, 10.1038/nmeth.3035]

[34] Dynamic CpG island methylation landscape in oocytes and preimplantation embryos [J].

Smallwood, Sebastien A. ;

Tomizawa, Shin-ichi ;

Krueger, Felix ;

Ruf, Nico ;

Carli, Natasha ;

Segonds-Pichon, Anne ;

Sato, Shun ;

Hata, Kenichiro ;

Andrews, Simon R. ;

Kelsey, Gavin .

NATURE GENETICS, 2011, 43 (08) :811-U126

[35] A unique regulatory phase of DNA methylation in the early mammalian embryo [J].

Smith, Zachary D. ;

Chan, Michelle M. ;

Mikkelsen, Tarjei S. ;

Gu, Hongcang ;

Gnirke, Andreas ;

Regev, Aviv ;

Meissner, Alexander .

NATURE, 2012, 484 (7394) :339-U74

[36] DNA-binding factors shape the mouse methylome at distal regulatory regions [J].

Stadler, Michael B. ;

Murr, Rabih ;

Burger, Lukas ;

Ivanek, Robert ;

Lienert, Florian ;

Schoeler, Anne ;

Wirbelauer, Christiane ;

Oakeley, Edward J. ;

Gaidatzis, Dimos ;

Tiwari, Vijay K. ;

Schuebeler, Dirk .

NATURE, 2011, 480 (7378) :490-495

[37] Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation [J].

Stegmaier, K ;

Ross, KN ;

Colavito, SA ;

O'Malley, S ;

Stockwell, BR ;

Golub, TR .

NATURE GENETICS, 2004, 36 (03) :257-263

[38] Tagmentation-based whole-genome bisulfite sequencing [J].

Wang, Qi ;

Gu, Lei ;

Adey, Andrew ;

Radlwimmer, Bernhard ;

Wang, Wei ;

Hovestadt, Volker ;

Baehr, Marion ;

Wolf, Stephan ;

Shendure, Jay ;

Eils, Roland ;

Plass, Christoph ;

Weichenhan, Dieter .

NATURE PROTOCOLS, 2013, 8 (10) :2022-2032

← 1 2 3 4 →