期刊
CELL REPORTS
卷 10, 期 8, 页码 1386-1397出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.02.001
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资金
- European Union [282510]
- ERA-NET project EpiMark (FWF grant) [I 1575-B19]
- ERA-NET project CINOCA (FWF grant) [I 1626-B22]
- European Molecular Biology Organization [ALTF 1431-2013]
- Human Frontier Science Program [LT000211/2014]
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.
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