ArticleProceedings of the National Academy of Sciences of the United States of America2023
Single-cell bisulfite-free 5mC and 5hmC sequencing with high sensitivity and scalability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Epigenetic regulation of humoral immunity: molecular mechanisms, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Combined epigenomic landscapes of 5mC, 5hmC, and 6mA modifications in papillary thyroid carcinogenesis.Communications biology · 2026Article
- Spatial 5mC-seq profiling of embryos and decidua after implantation in mammals.Nature methods · 2026Article
- DNA methylation meets lineage tracing: History, recent progress, and future directions.Quantitative biology (Beijing, China) · 2026Article
- Postnatal conversion of methylcytosine to hydroxymethylcytosine reconfigures the human neuronal epigenome.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in methodologies of epigenomics.Epigenomics · 2026Review
- Variations in Innate Immune Cell Subtypes Correlate with Epigenetic Clocks, Inflammaging and Health Outcomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- KnowYourCG: Facilitating base-level sparse methylome interpretation.Science advances · 2025Article
- DNA methylation and machine learning: challenges and perspective toward enhanced clinical diagnostics.Clinical epigenetics · 2025Review
- A ternary-code DNA methylome atlas of mouse tissues.Genome biology · 2025Article
- Article
- Whole-genome methylation profiling of extracellular vesicle DNA in gastric cancer identifies intercellular communication features.Nature communications · 2025Article
- A comprehensive guide to genomeZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Direct and bisulfite-free 5-methylcytosine and 5-hydroxymethylcytosine sequencing at single-cell resolution with scTAPS and scCAPS + .Genome biology · 2025Article
- High-coverage allele-resolved single-cell DNA methylation profiling reveals cell lineage, X-inactivation state, and replication dynamics.Nature communications · 2025Article
- Epigenetic ageing clocks: statistical methods and emerging computational challenges.Nature reviews. Genetics · 2025Review
- Advances and applications in single-cell and spatial genomics.Science China. Life sciences · 2025Review
- Cell-type-specific subtyping of epigenomes improves prognostic stratification of cancer.Genome medicine · 2025Article
- Elucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders.iScience · 2025Review
- 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation.Biomarker research · 2025Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging. Here, we present a bisulfite-free single-cell whole-genome 5mC and 5hmC profiling technique, named Cabernet, which can characterize 5mC and 5hmC at single-base resolution with high genomic coverage. Cabernet utilizes Tn5 transposome for DNA fragmentation, which enables the discrimination between different alleles for measuring hemi-methylation status. Using Cabernet, we revealed the 5mC, hemi-5mC and 5hmC dynamics during early mouse embryo development, uncovering genomic regions exclusively governed by active or passive demethylation. We show that hemi-methylation status can be used to distinguish between pre- and post-replication cells, enabling more efficient cell grouping when integrated with 5mC profiles. The property of Tn5 naturally enables Cabernet to achieve high-throughput single-cell methylome profiling, where we probed mouse cortical neurons and embryonic day 7.5 (E7.5) embryos, and constructed the library for thousands of single cells at high efficiency, demonstrating its potential for analyzing complex tissues at substantially low cost. Together, we present a way of high-throughput methylome and hydroxymethylome detection at single-cell resolution, enabling efficient analysis of the epigenetic status of biological systems with complicated nature such as neurons and cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.