ArticleNature cell biology2008
Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5.
Article in Nature cell biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 371 citations in OpenAlex.
- Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates.Frontiers in veterinary science · 2021Pooled it
- Gene regulation at the early human maternal-fetal interface.Nature reviews. Genetics · 2026Review
- DNA methylation reprogramming in marsupial embryos is restricted to the extraembryonic lineage.Nature communications · 2026Article
- IAPEz retrotransposons regulate the first lineage segregation in mouse pre-implantation development.Nucleic acids research · 2026Article
- Replication stress primes a trophectoderm fate in embryonic stem cells.Cell death discovery · 2026Article
- Loss of maternal PADI6 disrupts DNA methylation and genomic imprinting maintenance in late preimplantation mouse embryos.Epigenetics & chromatin · 2026Article
- DNA Methylation in the Ovary and Uterus of Mammalian Animal Models: Implications for Reproductive Function.Genes · 2026Review
- Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation.Protein & cell · 2026Article
- Divergent roles of DNA methylation, TRIM28, and p53 surveillance in human embryonic and trophoblast stem cells.bioRxiv : the preprint server for biology · 2025Article
- Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis.Stem cell reports · 2025Article
- Single-cell transcriptomics of organoids reveals transcriptional control of germline stem cell fate by an E2F1-TFAP2C-SOX17 positive-feedback loop in Turner syndrome.Cell & bioscience · 2025Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- Epigenetic control of cell identities from epiblast to gastrulation.The FEBS journal · 2025Review
- Self-organization of mouse embryonic stem cells into reproducible pre-gastrulation embryo models via CRISPRa programming.Cell stem cell · 2025Article
- The building blocks of embryo models: embryonic and extraembryonic stem cells.Cell discovery · 2025Review
- Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.Nature communications · 2025Article
- Revisiting trophectoderm-inner cell mass lineage segregation in the mammalian preimplantation embryo.Human reproduction (Oxford, England) · 2024Review
- KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.Nature communications · 2024Article
- Uncovering the role of TET2-mediated ENPEP activation in trophoblast cell fate determination.Cellular and molecular life sciences : CMLS · 2024Article
- The impact of DNA methylation on CTCF-mediated 3D genome organization.Nature structural & molecular biology · 2024Review
125 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mouse ES cells can differentiate into all three germ layers of the embryo but are generally excluded from the trophoblast lineage. Here we show that ES cells deficient in DNA methylation can differentiate efficiently into trophoblast derivatives. In a genome-wide screen we identified the transcription factor Elf5 as methylated and repressed in ES cells, and hypomethylated and expressed in TS and methylation-deficient ES cells. Elf5 creates a positive-feedback loop with the TS cell determinants Cdx2 and Eomes that is restricted to the trophoblast lineage by epigenetic regulation of Elf5. Importantly, the late-acting function of Elf5 allows initial plasticity and regulation in the early blastocyst. Thus, Elf5 functions as a gatekeeper, downstream of initial lineage determination, to reinforce commitment to the trophoblast lineage or to abort this pathway in epiblast cells. This epigenetic restriction of cell lineage fate provides a molecular mechanism for Waddington's concept of canalization of developmental pathways.
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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.