ArticleProceedings of the National Academy of Sciences of the United States of America2020
Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 157 citations in OpenAlex.
- Gene regulation at the early human maternal-fetal interface.Nature reviews. Genetics · 2026Review
- Hippo signaling regulates spontaneous human trophoblast syncytialization in three-dimensional cultures.Molecular human reproduction · 2026Article
- CHD8-Dependent Chromatin Licensing Sustains Trophoblast Stem Cell Transcriptional Programs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Combined EP300 and CREBBP Expression Levels Regulate Human Trophoblast Differentiation.International journal of molecular sciences · 2026Article
- Enzymatic activity-independent NANS stabilizes LATS2 to drive growth and therapeutic resistance in HR+/HER2- breast cancer.Nature communications · 2026Article
- aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.Stem cell reports · 2026Article
- Defective Trophoblast Differentiation, Endothelial Dysfunction, and Immune Dysregulation in Preeclampsia Coalesce on a Placental VGLL3-Centered Gene Network.Circulation · 2026Article
- Single-cell insights into trophoblast heterogeneity and adaptive dysfunction in selective fetal growth restriction.Communications biology · 2026Article
- Trophoblast Fusion Deficiency in Placenta-Related Pregnancy Disorders.Advances in experimental medicine and biology · 2026Review
- VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- The role of the striatin family proteins in hippo signaling and cellular regulation.Cell & bioscience · 2025Article
- Article
- VGLL3-centered network connects placental, vascular, and immune defects in preeclampsia.bioRxiv : the preprint server for biology · 2025Article
- Hippo signaling in mammalian reproduction.Reproduction (Cambridge, England) · 2025Review
- SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs.Scientific reports · 2025Article
- Dysregulation of MYBL2 impairs extravillous trophoblast lineage development and function, contributing to recurrent spontaneous abortion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The multifaceted roles of the transcriptional coactivator TAZ in extravillous trophoblast development of the human placenta.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The TEA domain transcription factors TEAD1 and TEAD3 and WNT signaling determine HLA-G expression in human extravillous trophoblasts.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Trophoblast Fusion in Hypertensive Disorders of Pregnancy and Preeclampsia.International journal of molecular sciences · 2025Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Various pregnancy complications, such as severe forms of preeclampsia or intrauterine growth restriction, are thought to arise from failures in the differentiation of human placental trophoblasts. Progenitors of the latter either develop into invasive extravillous trophoblasts, remodeling the uterine vasculature, or fuse into multinuclear syncytiotrophoblasts transporting oxygen and nutrients to the growing fetus. However, key regulatory factors controlling trophoblast self-renewal and differentiation have been poorly elucidated. Using primary cells, three-dimensional organoids, and CRISPR-Cas9 genome-edited JEG-3 clones, we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of cytotrophoblast progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15. Genome-wide comparisons of primary villous cytotrophoblasts overexpressing constitutively active YAP-5SA with YAP KO cells and syncytializing trophoblasts revealed common target genes involved in trophoblast stemness and differentiation. ChIP-qPCR unraveled that YAP-5SA overexpression increased binding of YAP-TEAD4 complexes to promoters of proliferation-associated genes such as
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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.