ArticleNature biotechnology2016
Single-cell 5hmC sequencing reveals chromosome-wide cell-to-cell variability and enables lineage reconstruction.
Article in Nature biotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed.
- DNA methylation meets lineage tracing: History, recent progress, and future directions.Quantitative biology (Beijing, China) · 2026Article
- Advances in CRISPR-Cas9 in lineage tracing of model animals.Animal models and experimental medicine · 2025Review
- 5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target.Clinical and translational medicine · 2025Article
- Simultaneous single-cell analysis of 5mC and 5hmC with SIMPLE-seq.Nature biotechnology · 2025Article
- Single-cell omics: experimental workflow, data analyses and applications.Science China. Life sciences · 2025Review
- 5hmC-profiles in Puerto Rican Hispanic/Latino men with aggressive prostate cancer.Frontiers in oncology · 2025Article
- Single-cell multi-omics in the study of digestive system cancers.Computational and structural biotechnology journal · 2024Review
- Application of Single Cell Methods in Immunometabolism and Immunotoxicology.Current opinion in toxicology · 2024Article
- Review
- Combinatorial quantification of 5mC and 5hmC at individual CpG dyads and the transcriptome in single cells reveals modulators of DNA methylation maintenance fidelity.Nature structural & molecular biology · 2024Article
- Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.Nature communications · 2024Article
- Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects.Nature biotechnology · 2024Article
- Applications of single‑cell omics and spatial transcriptomics technologies in gastric cancer (Review).Oncology letters · 2024Review
- Single-cell analysis of the epitranscriptome: RNA modifications under the microscope.RNA biology · 2024Review
- Single-cell sequencing technology applied to epigenetics for the study of tumor heterogeneity.Clinical epigenetics · 2023Review
- DARESOME enables concurrent profiling of multiple DNA modifications with restriction enzymes in single cells and cell-free DNA.Science advances · 2023Article
- Neuropsychiatric features in a multi-ethnic population with Alzheimer disease and mild cognitive impairment.International journal of geriatric psychiatry · 2023Article
- Liquid biopsies for cancer: From bench to clinic.MedComm · 2023Review
- Interpreting non-coding disease-associated human variants using single-cell epigenomics.Nature reviews. Genetics · 2023Review
- Mammalian DNA methylome dynamics: mechanisms, functions and new frontiers.Development (Cambridge, England) · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epigenetic DNA modification 5-hydroxymethylcytosine (5hmC) has crucial roles in development and gene regulation. Quantifying the abundance of this epigenetic mark at the single-cell level could enable us to understand its roles. We present a single-cell, genome-wide and strand-specific 5hmC sequencing technology, based on 5hmC glucosylation and glucosylation-dependent digestion of DNA, that reveals pronounced cell-to-cell variability in the abundance of 5hmC on the two DNA strands of a given chromosome. We develop a mathematical model that reproduces the strand bias and use this model to make two predictions. First, the variation in strand bias should decrease when 5hmC turnover increases. Second, the strand bias of two sister cells should be strongly anti-correlated. We validate these predictions experimentally, and use our model to reconstruct lineages of two- and four-cell mouse embryos, showing that single-cell 5hmC sequencing can be used as a lineage reconstruction tool.
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