ArticleProceedings of the National Academy of Sciences of the United States of America2022
Hippo signaling cofactor, WWTR1, at the crossroads of human trophoblast progenitor self-renewal and differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- 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
- An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Arginine methyltransferase PRMT1 equipoises trophoblast development to prevent early pregnancy loss.Nature communications · 2026Article
- Defective Trophoblast Differentiation, Endothelial Dysfunction, and Immune Dysregulation in Preeclampsia Coalesce on a Placental VGLL3-Centered Gene Network.Circulation · 2026Article
- Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures.bioRxiv : the preprint server for biology · 2026Article
- Maternal microRNAs linked to birth deficits due to prenatal alcohol exposure are dominant modifiers of gene expression in invasive trophoblast cells.Frontiers in cell and developmental biology · 2026Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- Parity modifies the effect of genetic variants associated with gestational duration and birth weight.medRxiv : the preprint server for health sciences · 2025Article
- 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
- Maternal plasma extracellular vesicles tsRNA as potential biomarkers for assessing preterm labor risk.BMC pregnancy and childbirth · 2025Article
- Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases.Nature communications · 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
- Trophoblast Fusion in Hypertensive Disorders of Pregnancy and Preeclampsia.International journal of molecular sciences · 2025Review
- Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.Nature communications · 2025Article
- Article
- Review
- Whole-Genome Resequencing to Identify Selection Signatures Associated with High Fertility in Lüliang Black Goat.Animals : an open access journal from MDPI · 2024Article
- Single-cell and spatial transcriptomics: Discovery of human placental development and disease.FASEB bioAdvances · 2024Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Healthy progression of human pregnancy relies on cytotrophoblast (CTB) progenitor self-renewal and its differentiation toward multinucleated syncytiotrophoblasts (STBs) and invasive extravillous trophoblasts (EVTs). However, the underlying molecular mechanisms that fine-tune CTB self-renewal or direct its differentiation toward STBs or EVTs during human placentation are poorly defined. Here, we show that Hippo signaling cofactor WW domain containing transcription regulator 1 (WWTR1) is a master regulator of trophoblast fate choice during human placentation. Using human trophoblast stem cells (human TSCs), primary CTBs, and human placental explants, we demonstrate that WWTR1 promotes self-renewal in human CTBs and is essential for their differentiation to EVTs. In contrast, WWTR1 prevents induction of the STB fate in undifferentiated CTBs. Our single-cell RNA sequencing analyses in first-trimester human placenta, along with mechanistic analyses in human TSCs revealed that WWTR1 fine-tunes trophoblast fate by directly regulating WNT signaling components. Importantly, our analyses of placentae from pathological pregnancies show that extreme preterm births (gestational time ≤28 wk) are often associated with loss of WWTR1 expression in CTBs. In summary, our findings establish the critical importance of WWTR1 at the crossroads of human trophoblast progenitor self-renewal versus differentiation. It plays positive instructive roles in promoting CTB self-renewal and EVT differentiation and safeguards undifferentiated CTBs from attaining the STB fate.
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