• Medientyp: E-Artikel
  • Titel: GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency
  • Beteiligte: Krendl, Christian; Shaposhnikov, Dmitry; Rishko, Valentyna; Ori, Chaido; Ziegenhain, Christoph; Sass, Steffen; Simon, Lukas; Müller, Nikola S.; Straub, Tobias; Brooks, Kelsey E.; Chavez, Shawn L.; Enard, Wolfgang; Theis, Fabian J.; Drukker, Micha
  • Erschienen: Proceedings of the National Academy of Sciences, 2017
  • Erschienen in: Proceedings of the National Academy of Sciences
  • Sprache: Englisch
  • DOI: 10.1073/pnas.1708341114
  • ISSN: 0027-8424; 1091-6490
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  • Beschreibung: <jats:title>Significance</jats:title> <jats:p> This study provides a mechanistic explanation for the differentiation of trophoblasts from human pluripotent stem cells, a process relying on BMP morphogens. We found that a network of the transcription factors GATA2, GATA3, TFAP2A, and TFAP2C regulates early trophoblast progenitor specification by activating placental genes and inhibiting the pluripotency gene <jats:italic>OCT4</jats:italic> , thus acting to couple trophoblast specification with exit from pluripotency. To demonstrate the relevance of our findings in vivo, we show that down-regulating <jats:italic>GATA3</jats:italic> in primate embryos prevents trophectoderm specification. In addition, we present a genome-wide analysis of active and inactive chromatin during trophoblast progenitor specification. These results provide a basis to guide investigations of human trophectoderm development. </jats:p>
  • Zugangsstatus: Freier Zugang