ArticlePLoS computational biology2018
Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Molecular underpinnings of induced degenerative heterogeneity in the retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity.Autophagy · 2023Article
- Whole-Genome DNA Methylation Dynamics of Sheep Preimplantation Embryo Investigated by Single-Cell DNA Methylome Sequencing.Frontiers in genetics · 2021Article
- CGGBP1-regulated cytosine methylation at CTCF-binding motifs resists stochasticity.BMC genetics · 2020Article
- Enhanced single-cell metabolomics by capillary electrophoresis electrospray ionization-mass spectrometry with field amplified sample injection.Analytica chimica acta · 2020Article
- Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome.Genome biology · 2020Article
- Virtual methylome dissection facilitated by single-cell analyses.Epigenetics & chromatin · 2019Article
- Retinal-input-induced epigenetic dynamics in the developing mouse dorsal lateral geniculate nucleus.Epigenetics & chromatin · 2019Article
- Recursive Motif Analyses Identify Brain Epigenetic Transcription Regulatory Modules.Computational and structural biotechnology journal · 2019Article
- HeteroMeth: A Database of Cell-to-cell Heterogeneity in DNA Methylation.Genomics, proteomics & bioinformatics · 2018Article
- An Insight into the Difficulties in the Discovery of Specific Biomarkers of Limbal Stem Cells.International journal of molecular sciences · 2018Review
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Authors and funding
7 authors.
Funding
Abstract
Embryonic stem cells (ESCs) consist of a population of self-renewing cells displaying extensive phenotypic and functional heterogeneity. Research towards the understanding of the epigenetic mechanisms underlying the heterogeneity among ESCs is still in its initial stage. Key issues, such as how to identify cell-subset specifically methylated loci and how to interpret the biological meanings of methylation variations remain largely unexplored. To fill in the research gap, we implemented a computational pipeline to analyze single-cell methylome and to perform an integrative analysis with single-cell transcriptome data. According to the origins of variation in DNA methylation, we determined the genomic loci associated with allelic-specific methylation or asymmetric DNA methylation, and explored a beta mixture model to infer the genomic loci exhibiting cell-subset specific methylation (CSM). We observed that the putative CSM loci in ESCs are significantly enriched in CpG island (CGI) shelves and regions with histone marks for promoter and enhancer, and the genes hosting putative CSM loci show wide-ranging expression among ESCs. More interestingly, the putative CSM loci may be clustered into co-methylated modules enriching the binding motifs of distinct sets of transcription factors. Taken together, our study provided a novel tool to explore single-cell methylome and transcriptome to reveal the underlying transcriptional regulatory networks associated with epigenetic heterogeneity of ESCs.
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