ArticleStem cells and development2011
Paracrine and epigenetic control of trophectoderm differentiation from human embryonic stem cells: the role of bone morphogenic protein 4 and histone deacetylases.
Article in Stem cells and development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- BMP4 and FGF2 promote heterogeneous priming including extraembryonic lineages in porcine expanded potential stem cells.Frontiers in cell and developmental biology · 2026Article
- iPSC-based modeling of preeclampsia identifies epigenetic defects in extravillous trophoblast differentiation.iScience · 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
- Current Strategies of Modeling Human Trophoblast Using Human Pluripotent Stem Cells in vitro.Current protocols · 2023Article
- Article
- Intrauterine hyperglycemia impairs endometrial receptivity via up-regulating SGK1 in diabetes.Science China. Life sciences · 2022Article
- The role of BMP4 signaling in trophoblast emergence from pluripotency.Cellular and molecular life sciences : CMLS · 2022Review
- Modeling human peri-implantation placental development and function†.Biology of reproduction · 2021Review
- Modeling preeclampsia using human induced pluripotent stem cells.Scientific reports · 2021Article
- Generation of Trophoblast-Like Cells From Hypomethylated Porcine Adult Dermal Fibroblasts.Frontiers in veterinary science · 2021Article
- A Two-Step Protocol to Erase Human Skin Fibroblasts and Convert Them into Trophoblast-like Cells.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Human placenta and trophoblast development: key molecular mechanisms and model systems.Cellular and molecular life sciences : CMLS · 2019Review
- An Improved Two-Step Protocol for Trophoblast Differentiation of Human Pluripotent Stem Cells.Current protocols in stem cell biology · 2019Article
- Do locally advanced and metastatic human epithelial cancers evolve in 'placental/decidual-like microenvironments'?Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling.Cell death & disease · 2018Article
- Specification of trophoblast from embryonic stem cells exposed to BMP4.Biology of reproduction · 2018Review
- Primordial germ cell-like cells derived from canine adipose mesenchymal stem cells.Cell proliferation · 2016Article
- Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Our understanding of paracrine and epigenetic control of trophectoderm (TE) differentiation is limited by available models of preimplantation human development. Simple, defined media for selective TE differentiation of human embryonic stem cells (hESCs) were developed, enabling mechanistic studies of early placental development. Paracrine requirements of preimplantation human development were evaluated with hESCs by measuring lineage-specific transcription factor expression levels in single cells and morphological transformation in response to selected paracrine and epigenetic modulators. Bone morphogenic protein 4 (BMP4) addition to feeder-free pluripotent stem cells on matrigel frequently formed CDX2-positive TE. However, BMP4 or activin A inhibition alone also produced a mix of mesoderm and extraembryonic endoderm under these conditions. Further, BMP4 failed to form TE from adherent hESC maintained in standard feeder-dependent monolayers. Given that the efficiency and selectivity of BMP4-induced TE depended on medium components, we developed a basal medium containing insulin and heparin. In this medium, BMP4 induction of TE was dose dependent and with activin A inhibition by SB431542 (SB), approached 100% of cells. This paracrine stimulation of pluripotent cells transformed colony morphology from a cuboidal to squamous epithelium quantitatively on day 3, and produced significant multinucleated syncytiotrophoblasts by day 8. Addition of trichostatin A, a histone deacetylase (HDAC) inhibitor, reduced HDAC3, histone H3K9 methylation, and slowed differentiation in a dose-dependent manner. Modulators of BMP4- or HDAC-dependent signaling might adversely influence the timing and viability of early blastocyst developed in vitro. Since blastocyst development is synchronized to uterine receptivity, epigenetic regulators of TE differentiation might adversely affect implantation in vivo.
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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.