ArticleDevelopment (Cambridge, England)2013
BMP4-directed trophoblast differentiation of human embryonic stem cells is mediated through a ΔNp63+ cytotrophoblast stem cell state.
Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 136 citations in OpenAlex.
- Patient-specific trophoblast stem cells for placental medicine.Trends in molecular medicine · 2026Review
- Arginine methyltransferase PRMT1 equipoises trophoblast development to prevent early pregnancy loss.Nature communications · 2026Article
- Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.Human reproduction update · 2026Review
- HAND1 controls the lineage bifurcation of trophoblast and amnion from human pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2026Article
- Fine-tuning ERK activity enables proliferation-differentiation balance during lineage specification of human embryonic stem cells.PLoS biology · 2026Article
- 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
- Primed human pluripotent stem cell-derived blastocyst-like cell aggregates with partial lineage specification.Regenerative therapy · 2025Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- Stepwise strategy for generating human trophoblast stem-like cells from embryonic stem cells reveals specific role of TFAP2C in acquiring self-renewability.Scientific reports · 2025Article
- The modeling of human implantation and early placentation: achievements and perspectives.Human reproduction update · 2025Review
- Identification of HTRA4 as a Transcriptional Target of p63 in Trophoblast.The American journal of pathology · 2024Article
- Combinatorial interpretation of BMP and WNT controls the decision between primitive streak and extraembryonic fates.Cell systems · 2024Article
- Conserved and divergent features of trophoblast stem cells.Journal of molecular endocrinology · 2024Review
- iPSC-based modeling of preeclampsia identifies epigenetic defects in extravillous trophoblast differentiation.iScience · 2024Article
- Chimerization of human ESC-derived extraembryonic cells with the mouse blastocyst.International journal of biological sciences · 2024Article
- Comparison of Four Protocols for In Vitro Differentiation of Human Embryonic Stem Cells into Trophoblast Lineages by BMP4 and Dual Inhibition of Activin/Nodal and FGF2 Signaling.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Human fetal tissue is critical for biomedical research.Stem cell reports · 2023Review
- Current Strategies of Modeling Human Trophoblast Using Human Pluripotent Stem Cells in vitro.Current protocols · 2023Article
- Article
- Pluripotency-independent induction of human trophoblast stem cells from fibroblasts.Nature communications · 2023Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The placenta is a transient organ that is necessary for proper fetal development. Its main functional component is the trophoblast, which is derived from extra-embryonic ectoderm. Little is known about early trophoblast differentiation in the human embryo, owing to lack of a proper in vitro model system. Human embryonic stem cells (hESCs) differentiate into functional trophoblast following BMP4 treatment in the presence of feeder-conditioned media; however, this model has not been widely accepted, in part owing to a lack of proof for a trophoblast progenitor population. We have previously shown that p63, a member of the p53 family of nuclear proteins, is expressed in proliferative cytotrophoblast (CTB), precursors to terminally differentiated syncytiotrophoblast (STB) in chorionic villi and extravillous trophoblast (EVT) at the implantation site. Here, we show that BMP4-treated hESCs differentiate into bona fide CTB by direct comparison with primary human placental tissues and isolated CTB through gene expression profiling. We show that, in primary CTB, p63 levels are reduced as cells differentiate into STB, and that forced expression of p63 maintains cyclin B1 and inhibits STB differentiation. We also establish that, similar to in vivo events, hESC differentiation into trophoblast is characterized by a p63(+)/KRT7(+) CTB stem cell state, followed by formation of functional KLF4(+) STB and HLA-G(+) EVT. Finally, we illustrate that downregulation of p63 by shRNA inhibits differentiation of hESCs into functional trophoblast. Taken together, our results establish that BMP4-treated hESCs are an excellent model of human trophoblast differentiation, closely mimicking the in vivo progression from p63(+) CTB stem cells to terminally differentiated trophoblast subtypes.
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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.