ArticleGenome biology2016
Single-cell genome-wide bisulfite sequencing uncovers extensive heterogeneity in the mouse liver methylome.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed.
- Multiplexed single-cell reduced representation bisulfite sequencing for genome-wide DNA methylation profiling.Nature protocols · 2026Review
- DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications.Genes & diseases · 2026Review
- DNA Methylation, Aging, and Cancer.Epigenomes · 2025Review
- Advances in Microfluidic Single-Cell RNA Sequencing and Spatial Transcriptomics.Micromachines · 2025Review
- estiMAge: development of a DNA methylation clock to estimate the methylation age of single cells.Bioinformatics advances · 2025Article
- Concurrent analysis of genome and transcriptome in one single cell.BMC research notes · 2024Article
- scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood.Nature communications · 2024Article
- Analyzing somatic mutations by single-cell whole-genome sequencing.Nature protocols · 2024Review
- Review
- Computational Methods for Single-cell DNA Methylome Analysis.Genomics, proteomics & bioinformatics · 2023Review
- Technologies and applications of single-cell DNA methylation sequencing.Theranostics · 2023Review
- Article
- Toxicoepigenetics and Environmental Health: Challenges and Opportunities.Chemical research in toxicology · 2022Review
- Epigenetics, DNA damage, and aging.The Journal of clinical investigation · 2022Review
- scTEM-seq: Single-cell analysis of transposable element methylation to link global epigenetic heterogeneity with transcriptional programs.Scientific reports · 2022Article
- scSPLAT, a scalable plate-based protocol for single cell WGBS library preparation.Scientific reports · 2022Article
- Spatial Multiomics Analysis Reveals Only Minor Genetic and Epigenetic Changes in Human Liver Cancer Stem-Like Cells Compared With Other Tumor Parenchymal Cells.Frontiers in cell and developmental biology · 2022Article
- Profiling epigenetic age in single cells.Nature aging · 2021Article
- Epigenetic Clock and Circadian Rhythms in Stem Cell Aging and Rejuvenation.Journal of personalized medicine · 2021Review
- Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing.Oncotarget · 2021Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundTransmission fidelity of CpG DNA methylation patterns is not foolproof, with error rates from less than 1 to well over 10 % per CpG site, dependent on preservation of the methylated or unmethylated state and the type of sequence. This suggests a fairly high chance of errors. However, the consequences of such errors in terms of cell-to-cell variation have never been demonstrated by experimentally measuring intra-tissue heterogeneity in an adult organism.
resultsWe employ single-cell DNA methylomics to analyze heterogeneity of genome-wide 5-methylcytosine (5mC) patterns within mouse liver. Our results indicate a surprisingly high level of heterogeneity, corresponding to an average epivariation frequency of approximately 3.3 %, with regions containing H3K4me1 being the most variable and promoters and CpG islands the most stable. Our data also indicate that the level of 5mC heterogeneity is dependent on genomic features. We find that non-functional sites such as repeat elements and introns are mostly unstable and potentially functional sites such as gene promoters are mostly stable.
conclusionsBy employing a protocol for whole-genome bisulfite sequencing of single cells, we show that the liver epigenome is highly unstable with an epivariation frequency in DNA methylation patterns of at least two orders of magnitude higher than somatic mutation frequencies.
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