ArticleGenes & development2015
Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 109 citations in OpenAlex.
- Derivation of Mouse Dome-Shaped Trophoblast Stem Cells With Low Heterogeneity From Blastocysts.Cell proliferation · 2026Article
- The imprinted Peg3 gene is a potent regulator of the DNA methylome in trophoblast cells.Stem cell reports · 2026Article
- Stable maintenance of MERVL-positive embryonic stem cells reveals sustained transcriptional programs and enhancer remodeling.The Journal of biological chemistry · 2026Article
- The integrated developmental stress response (ISR-DASR) shift reveals a functional transition from cellular to stem cell organismal adaptation.Scientific reports · 2026Article
- Maternal Med12 safeguards trophoblast pluripotency and placental development.Biology of reproduction · 2026Article
- Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis.Stem cell reports · 2025Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- A roadmap towards targeted differentiation of mouse trophoblast stem cells into cell types of the feto-maternal exchange surface.Stem cell research & therapy · 2025Article
- Self-organization of mouse embryonic stem cells into reproducible pre-gastrulation embryo models via CRISPRa programming.Cell stem cell · 2025Article
- Eomesodermin in conjunction with the BAF complex promotes expansion and invasion of the trophectoderm lineage.Nature communications · 2025Article
- Super-Enhancers in Placental Development and Diseases.Journal of developmental biology · 2025Review
- Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.Nature communications · 2025Article
- Review
- The involvement of Elf5 in regulating keratinocyte proliferation and differentiation processes in skin.PloS one · 2025Article
- TFAP2C is a key regulator of intrauterine trophoblast cell invasion and deep hemochorial placentation.JCI insight · 2024Article
- Cited2 is a key regulator of placental development and plasticity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos.Nature structural & molecular biology · 2024Article
- Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches.Genome research · 2024Article
- Self-organization of embryonic stem cells into a reproducible embryo model through epigenome editing.bioRxiv : the preprint server for biology · 2024Article
- Quiescence enables unrestricted cell fate in naive embryonic stem cells.Nature communications · 2024Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Elf5 is a transcription factor with pivotal roles in the trophoblast compartment, where it reinforces a trophoblast stem cell (TSC)-specific transcriptional circuit. However, Elf5 is also present in differentiating trophoblast cells that have ceased to express other TSC genes such as Cdx2 and Eomes. In the present study, we aimed to elucidate the context-dependent role of Elf5 at the interface between TSC self-renewal and the onset of differentiation. We demonstrate that precise levels of Elf5 are critical for normal expansion of the TSC compartment and embryonic survival, as Elf5 overexpression triggers precocious trophoblast differentiation. Through integration of protein interactome, transcriptome, and genome-wide chromatin immunoprecipitation data, we reveal that this abundance-dependent function is mediated through a shift in preferred Elf5-binding partners; in TSCs, Elf5 interaction with Eomes recruits Tfap2c to triply occupied sites at TSC-specific genes, driving their expression. In contrast, the Elf5 and Tfap2c interaction becomes predominant as their protein levels increase. This triggers binding to double- and single-occupancy sites that harbor the cognate Tfap2c motif, causing activation of the associated differentiation-promoting genes. These data place Elf5 at the center of a stoichiometry-sensitive transcriptional network, where it acts as a molecular switch governing the balance between TSC proliferation and differentiation.
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Registered trials
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