ArticleCell2015
A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 348 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
348 citing papers in PubMed, 682 citations in OpenAlex.
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Human primordial germ cell heterogeneity in vitro is associated with distinctive biological states.Cellular & molecular biology letters · 2026Article
- Integration of single-cell transcriptome of female early gonadal development in bovine, goats, and pigs.iScience · 2026Article
- Germline and Embryonic Mechanisms in the Epigenetic Inheritance of Neurodevelopmental and Cognitive Traits in Mammals.Biomolecules · 2026Review
- From germline immortality to somatic rejuvenation: Unlocking the ovarian blueprint for longevity.PLoS biology · 2026Article
- A Review of the Effects of Maternal and Paternal Obesity on Neurodevelopmental Disorders and Related Neurobiology in Rodent and Human Offspring.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Sex-specific multigenerational epigenetic responses to real-world chemical mixture exposure in an outbred sheep model.bioRxiv : the preprint server for biology · 2026Article
- A spatiotemporal transcriptomic atlas of porcine (Sus scrofa) female early gonadal development.Communications biology · 2026Article
- Reprogramming the inactive X chromosome: dynamics and insights from the germline.Biochemical Society transactions · 2026Review
- The road to restore male fertility using in vitro-derived germ cells.Human reproduction update · 2026Review
- Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026Review
- EZHIP in Pediatric Brain Tumors: From Epigenetic Mimicry to Therapeutic Vulnerabilities.International journal of molecular sciences · 2026Review
- High resolution multi-scale profiling of embryonic germ cell-like cell derivation reveals pluripotent state transitions in humans.Stem cell reports · 2026Article
- Genetic heritage of war: exploring transgenerational inheritance of PTSD and its molecular background.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Environmental and Genetic Perturbations of the Sperm Epigenome.Advances in experimental medicine and biology · 2026Review
- Intergenerational and transgenerational epigenetic mechanisms shaping livestock production and reproduction.The Journal of reproduction and development · 2026Review
- De-extinction of the Northern white rhinoceros (Ceratotherium simum cottoni).The Journal of reproduction and development · 2026Review
- Marsupial single-cell transcriptomics identifies temporal diversity in mammalian developmental programs.Developmental cell · 2025Article
- A primordial germ cell-like-cell platform enables CRISPRi screen for epigenetic fertility modifiers.EMBO reports · 2025Article
- Toward Understanding and Halting Legacies of Trauma.Biological psychiatry · 2025Review
288 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Resetting of the epigenome in human primordial germ cells (hPGCs) is critical for development. We show that the transcriptional program of hPGCs is distinct from that in mice, with co-expression of somatic specifiers and naive pluripotency genes TFCP2L1 and KLF4. This unique gene regulatory network, established by SOX17 and BLIMP1, drives comprehensive germline DNA demethylation by repressing DNA methylation pathways and activating TET-mediated hydroxymethylation. Base-resolution methylome analysis reveals progressive DNA demethylation to basal levels in week 5-7 in vivo hPGCs. Concurrently, hPGCs undergo chromatin reorganization, X reactivation, and imprint erasure. Despite global hypomethylation, evolutionarily young and potentially hazardous retroelements, like SVA, remain methylated. Remarkably, some loci associated with metabolic and neurological disorders are also resistant to DNA demethylation, revealing potential for transgenerational epigenetic inheritance that may have phenotypic consequences. We provide comprehensive insight on early human germline transcriptional network and epigenetic reprogramming that subsequently impacts human development and disease.
Indexed as
Identifiers
What OpenQuestion holds
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.