ArticleNature structural & molecular biology2024
DNA methylation restricts coordinated germline and neural fates in embryonic stem cell differentiation.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Rising Incidence and Mortality of Colorectal Cancer Among Younger Adults: A Population-Based Study in Taiwan, 1994-2018.International journal of cancer · 2026Article
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Epigenetic Perspectives on Maternal Gut Microbiota's Impact on Embryonic and Fetal Development.Comprehensive Physiology · 2026Review
- DNA Methylation: A Key Epigenetic Regulator of Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- In vitro approaches to study centriole and cilium function in early mouse embryogenesis.Life science alliance · 2026Article
- Antisense transcription can induce expression memory via stable promoter repression.Genome biology · 2025Article
- TET knockout cells transit between pluripotent states and exhibit precocious germline entry.The EMBO journal · 2025Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- DNA methylation shapes the Polycomb landscape during the exit from naive pluripotency.Nature structural & molecular biology · 2025Article
- [Research Progress in the Mechanisms of Acupuncture in Regulating DNA Methylation].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Chloral Hydrate's Impact on Brain Development: From Clinical Safety to Molecular Mechanisms.Drug design, development and therapy · 2025Review
- DNA methylation in mammalian development and disease.Nature reviews. Genetics · 2025Review
- Progress in Epigenetic Modification Regulating Drug Transporters in the Hypoxic Environment.Current drug delivery · 2025Review
- Epigenetics and the timing of neuronal differentiation.Current opinion in neurobiology · 2024Review
- The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation.Nucleic acids research · 2024Article
- Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- DNMT1 can induce primary germ layer differentiation through de novo DNA methylation.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Cross-tissue patterns of DNA hypomethylation reveal genetically distinct histories of cell development.BMC genomics · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As embryonic stem cells (ESCs) transition from naive to primed pluripotency during early mammalian development, they acquire high DNA methylation levels. During this transition, the germline is specified and undergoes genome-wide DNA demethylation, while emergence of the three somatic germ layers is preceded by acquisition of somatic DNA methylation levels in the primed epiblast. DNA methylation is essential for embryogenesis, but the point at which it becomes critical during differentiation and whether all lineages equally depend on it is unclear. Here, using culture modeling of cellular transitions, we found that DNA methylation-free mouse ESCs with triple DNA methyltransferase knockout (TKO) progressed through the continuum of pluripotency states but demonstrated skewed differentiation abilities toward neural versus other somatic lineages. More saliently, TKO ESCs were fully competent for establishing primordial germ cell-like cells, even showing temporally extended and self-sustained capacity for the germline fate. By mapping chromatin states, we found that neural and germline lineages are linked by a similar enhancer dynamic upon exit from the naive state, defined by common sets of transcription factors, including methyl-sensitive ones, that fail to be decommissioned in the absence of DNA methylation. We propose that DNA methylation controls the temporality of a coordinated neural-germline axis of the preferred differentiation route during early development.
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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.