ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
BHLHE40 Cooperates with GATA2/3 to Control Human Syncytiotrophoblast Lineage Differentiation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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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
3 citing papers in PubMed.
- CHD8-Dependent Chromatin Licensing Sustains Trophoblast Stem Cell Transcriptional Programs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reduced FBXO22 skews human trophoblast fate equilibrium toward syncytialization via polyubiquitinating the CoREST complex.Nucleic acids research · 2026Article
- BHLHE40 Cooperates with GATA2/3 to Control Human Syncytiotrophoblast Lineage Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Syncytiotrophoblasts (STBs) constitute one of the core components of the placenta, responsible for synthesizing pregnancy-sustaining hormones such as human chorionic gonadotropin (HCG). Deficient syncytialization of cytotrophoblasts affects the hormonal secretion and placental development, contributing to pregnancy-associated disorders, including spontaneous miscarriage. To date, the molecular mechanisms, particularly the role of transcription factors (TFs), in STB lineage specification remain incompletely understood. Through targeting direct regulators of a STB lineage-specific marker, CGB (encoding chorionic gonadotropin-β), by DNA pull-down coupled with mass spectrometry, basic helix-loop-helix family member 40 (BHLHE40) has been identified as a key regulator in human STB differentiation. BHLHE40 expression is increased during STB differentiation but reduced in villous samples from women with miscarriages. CRISPR/Cas9-mediated knockout of BHLHE40 in human trophoblast stem cells (TSCs) prevents STB differentiation in vitro, impairing gene expression critical for hormone synthesis and cell syncytialization. Mechanistically, BHLHE40 interacts directly with GATA2 and GATA3 to facilitate their chromatin occupancy, thereby activating transcriptional programs essential for STB differentiation. These findings uncover a BHLHE40-GATA2/3 regulatory network governing human trophoblast lineage commitment, providing insights into placental development and potential therapeutic targets for pregnancy disorders.
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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 Socratic graph.