Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics

Cell Reports
Matthias FarlikChristoph Bock

Abstract

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 (μWGBS) 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.

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Jan 12, 2016·Nature Methods·Christof AngermuellerWolf Reik
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Methods Mentioned

BETA
WGBS
RRBS
PCR
fluorescence-activated cell sorting
FACS
MDS
scRRBS
methylome sequencing
FCS
Methyl-Seq

Software Mentioned

scWGBS
scPBAT
Bismark Bisulfite Mapper
RnBeads
Bismark
Trimmomatic
R
EpiExplorer

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