ArticleProceedings of the National Academy of Sciences of the United States of America2016
Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 160 citations in OpenAlex.
- Patient-specific trophoblast stem cells for placental medicine.Trends in molecular medicine · 2026Review
- Building Disease Models for Endometriosis: iPSCs as Game-Changers.International journal of molecular sciences · 2026Review
- Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.Human reproduction update · 2026Review
- Endogenous VEGF signaling acts as a guardian of human primed pluripotency.Nature communications · 2026Article
- Engineering the Human Endometrial-Embryo Interface: Breakthroughs in 3D Uterine Models.Biomolecules · 2026Review
- Personalized Models of Biological Barriers and Their Diseases: Recent Progress with Organs-On-Chips.Advanced 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
- Manifold roles of the chemokine G-protein-coupled receptor CCR7 in differentiation of human trophoblast into extravillous and syncytiotrophoblast lineages.Development (Cambridge, England) · 2025Article
- Models of Endocrine-Disrupting Effects: Human Placental Steroidogenesis.Basic & clinical pharmacology & toxicology · 2025Review
- In vitro differentiation of macaque extravillous trophoblasts in a low oxygen environment.Placenta · 2025Article
- The modeling of human implantation and early placentation: achievements and perspectives.Human reproduction update · 2025Review
- Strategy advancements in placental pharmacokinetics: fromFrontiers in pharmacology · 2025Review
- Generation of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells.International journal of molecular sciences · 2024Article
- The impact of dynamic caudal type homeobox 2 expression on the differentiation of human trophoblast lineage during implantation.Cell proliferation · 2024Article
- Transplacental SARS-CoV-2 protein ORF8 binds to complement C1q to trigger fetal inflammation.The EMBO journal · 2024Article
- Highly efficient generation of self-renewing trophoblast from human pluripotent stem cells.iScience · 2024Article
- Rapid retinoic acid-induced trophoblast cell model from human induced pluripotent stem cells.Scientific reports · 2024Article
- KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.Nature communications · 2024Article
- iPSC-based modeling of preeclampsia identifies epigenetic defects in extravillous trophoblast differentiation.iScience · 2024Article
- Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine.Current medicinal chemistry · 2024Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Trophoblast is the primary epithelial cell type in the placenta, a transient organ required for proper fetal growth and development. Different trophoblast subtypes are responsible for gas/nutrient exchange (syncytiotrophoblasts, STBs) and invasion and maternal vascular remodeling (extravillous trophoblasts, EVTs). Studies of early human placental development are severely hampered by the lack of a representative trophoblast stem cell (TSC) model with the capacity for self-renewal and the ability to differentiate into both STBs and EVTs. Primary cytotrophoblasts (CTBs) isolated from early-gestation (6-8 wk) human placentas are bipotential, a phenotype that is lost with increasing gestational age. We have identified a CDX2(+)/p63(+) CTB subpopulation in the early postimplantation human placenta that is significantly reduced later in gestation. We describe a reproducible protocol, using defined medium containing bone morphogenetic protein 4 by which human pluripotent stem cells (hPSCs) can be differentiated into CDX2(+)/p63(+) CTB stem-like cells. These cells can be replated and further differentiated into STB- and EVT-like cells, based on marker expression, hormone secretion, and invasive ability. As in primary CTBs, differentiation of hPSC-derived CTBs in low oxygen leads to reduced human chorionic gonadotropin secretion and STB-associated gene expression, instead promoting differentiation into HLA-G(+) EVTs in an hypoxia-inducible, factor-dependent manner. To validate further the utility of hPSC-derived CTBs, we demonstrated that differentiation of trisomy 21 (T21) hPSCs recapitulates the delayed CTB maturation and blunted STB differentiation seen in T21 placentae. Collectively, our data suggest that hPSCs are a valuable model of human placental development, enabling us to recapitulate processes that result in both normal and diseased pregnancies.
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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.