ArticleProceedings of the National Academy of Sciences of the United States of America2013
Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
163 citing papers in PubMed, 278 citations in OpenAlex.
- Patient-specific trophoblast stem cells for placental medicine.Trends in molecular medicine · 2026Review
- Review
- Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.Human reproduction update · 2026Review
- Synthetic embryos: current progress, application and challenges.Reproductive biology and endocrinology : RB&E · 2026Review
- Endogenous VEGF signaling acts as a guardian of human primed pluripotency.Nature communications · 2026Article
- HAND1 controls the lineage bifurcation of trophoblast and amnion from human pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2026Article
- Progress in stem cell-based embryo models and their applications in developmental biology and biomedicine.Nature reviews. Molecular cell 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
- Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis.Stem cell reports · 2025Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- 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
- Two classes of syncytiotrophoblast nuclei form following BAP-driven human pluripotent stem cell differentiation.Placenta · 2025Article
- Fluorescence-activated nuclear sorting (FANS) of nuclei from in vitro-generated syncytiotrophoblast.Placenta · 2025Article
- Stem cell-based embryo models: a tool to study early human development.Science China. Life sciences · 2025Review
- Chromosomal instability in human trophoblast stem cells and placentas.Nature communications · 2025Article
- HAND1, partially mediated through ape-specific LTR binding, is essential for human extra-embryonic mesenchyme derivation from iPSCs.Cell reports · 2025Article
- The building blocks of embryo models: embryonic and extraembryonic stem cells.Cell discovery · 2025Review
- Transient chemical-mediated epigenetic modulation confers unrestricted lineage potential on human primed pluripotent stem cells.Science China. Life sciences · 2025Article
- Development of apical out trophoblast stem cell derived organoids to model early human pregnancy.iScience · 2025Article
- The modeling of human implantation and early placentation: achievements and perspectives.Human reproduction update · 2025Review
103 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Human ES cells (hESC) exposed to bone morphogenic protein 4 (BMP4) in the absence of FGF2 have become widely used for studying trophoblast development, but the soundness of this model has been challenged by others, who concluded that differentiation was primarily toward mesoderm rather than trophoblast. Here we confirm that hESC grown under the standard conditions on a medium conditioned by mouse embryonic fibroblasts in the presence of BMP4 and absence of FGF2 on a Matrigel substratum rapidly convert to an epithelium that is largely KRT7(+) within 48 h, with minimal expression of mesoderm markers, including T (Brachyury). Instead, they begin to express a series of trophoblast markers, including HLA-G, demonstrate invasive properties that are independent of the continued presence of BMP4 in the medium, and, over time, produce extensive amounts of human chorionic gonadotropin, progesterone, placental growth factor, and placental lactogen. This process of differentiation is not dependent on conditioning of the medium by mouse embryonic fibroblasts and is accelerated in the presence of inhibitors of Activin and FGF2 signaling, which at day 2 provide colonies that are entirely KRT7(+) and in which the majority of cells are transiently CDX2(+). Colonies grown on two chemically defined media, including the one in which BMP4 was reported to drive mesoderm formation, also differentiate at least partially to trophoblast in response to BMP4. The experiments demonstrate that the in vitro BMP4/hESC model is valid for studying the emergence and differentiation of trophoblasts.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.