ArticleProceedings of the National Academy of Sciences of the United States of America2024
NOTUM-mediated WNT silencing drives extravillous trophoblast cell lineage development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- PPARG directs trophoblast cell fate and establishment of the uterine-placental interface.EMBO reports · 2026Article
- Combined EP300 and CREBBP Expression Levels Regulate Human Trophoblast Differentiation.International journal of molecular sciences · 2026Article
- Spleen-associated macrophage alterations and embryo viability in a murine model of recurrent spontaneous abortion.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Single-nucleus multi-omics dissection of dysregulated trophoblast development and disrupted immune microenvironment in complete hydatidiform moles.Science China. Life sciences · 2026Article
- Cross-species insights into placental evolution and diseases at the single-cell resolution.Nature communications · 2026Article
- Unlocking Wnt's weak spot: Glycosylated nanoalbumins to reignite immune responses in MSS-CRC.Journal of pharmaceutical analysis · 2026Article
- Distinct transcriptional and epigenomic programs define Hofbauer cells in term placenta.JCI insight · 2026Article
- Transient inhibition of MEK/ERK and WNT pathways enhances direct differentiation of primed hPSCs into functional trophoblast stem cells.Cell regeneration (London, England) · 2026Article
- Trophoblast-derived proteins and their effects on the pathogenesis of preeclampsia.Histology and histopathology · 2026Review
- The lncRNA GAS5-encoded micropeptide facilitates influenza virus replication through modulation of the Wnt/β-catenin signaling pathway.Current research in microbial sciences · 2026Article
- Characterization of the tumor microenvironment in locally advanced gastric cancer and identification of spatially predictive biomarkers associated with beneficial neoadjuvant immunochemotherapy.Frontiers in immunology · 2026Article
- Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025Review
- TCF7L2 is essential for the differentiation and invasive function of human extravillous trophoblast.Cellular and molecular life sciences : CMLS · 2025Article
- Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion.Genes & diseases · 2025Article
- PPARG directs trophoblast cell fate and establishment of the uterine-placental interface.bioRxiv : the preprint server for biology · 2025Article
- WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm.Journal of cell science · 2025Article
- Manifold roles of the chemokine G-protein-coupled receptor CCR7 in differentiation of human trophoblast into extravillous and syncytiotrophoblast lineages.Development (Cambridge, England) · 2025Article
- Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion.Cells · 2025Article
- Effects of an aryl hydrocarbon receptor ligand on human trophoblast cell development.Human reproduction (Oxford, England) · 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
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Abstract
Trophoblast stem (TS) cells have the unique capacity to differentiate into specialized cell types, including extravillous trophoblast (EVT) cells. EVT cells invade into and transform the uterus where they act to remodel the vasculature facilitating the redirection of maternal nutrients to the developing fetus. Disruptions in EVT cell development and function are at the core of pregnancy-related disease. WNT-activated signal transduction is a conserved regulator of morphogenesis of many organ systems, including the placenta. In human TS cells, activation of canonical WNT signaling is critical for maintenance of the TS cell stem state and its downregulation accompanies EVT cell differentiation. We show that aberrant WNT signaling undermines EVT cell differentiation. Notum, palmitoleoyl-protein carboxylesterase (NOTUM), a negative regulator of canonical WNT signaling, was prominently expressed in first-trimester EVT cells developing in situ and up-regulated in EVT cells derived from human TS cells. Furthermore, NOTUM was required for optimal human TS cell differentiation to EVT cells. Activation of NOTUM in EVT cells is driven, at least in part, by endothelial Per-Arnt-Sim (PAS) domain 1 (also called hypoxia-inducible factor 2 alpha). Collectively, our findings indicate that canonical Wingless-related integration site (WNT) signaling is essential for maintenance of human trophoblast cell stemness and regulation of human TS cell differentiation. Downregulation of canonical WNT signaling via the actions of NOTUM is required for optimal EVT cell differentiation.
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