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GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency.
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.
Afiliación
  • Krendl C; Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Shaposhnikov D; Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Rishko V; Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Ori C; Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Ziegenhain C; Anthropology and Human Genomics, Department of Biology II, Ludwig-Maximilians University Munich, 82152 Martinsried, Germany.
  • Sass S; Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Simon L; Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Müller NS; Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Straub T; Biomedical Center, Core Facility Bioinformatics, Ludwig-Maximilians University Munich, 82152 Martinsried, Germany.
  • Brooks KE; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006.
  • Chavez SL; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006.
  • Enard W; Anthropology and Human Genomics, Department of Biology II, Ludwig-Maximilians University Munich, 82152 Martinsried, Germany.
  • Theis FJ; Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany.
  • Drukker M; Department of Mathematics, Technical University Munich, 85748 Garching, Germany.
Proc Natl Acad Sci U S A ; 114(45): E9579-E9588, 2017 11 07.
Article en En | MEDLINE | ID: mdl-29078328
To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined them with the temporally resolved transcriptome of the preprogenitor phase and of single APA+ cells. This revealed a circuit of bivalent TFAP2A, TFAP2C, GATA2, and GATA3 transcription factors, coined collectively the "trophectoderm four" (TEtra), which are also present in human trophectoderm in vivo. At the onset of differentiation, the TEtra factors occupy multiple sites in epigenetically inactive placental genes and in OCT4 Functional manipulation of GATA3 and TFAP2A indicated that they directly couple trophoblast-specific gene induction with suppression of pluripotency. In accordance, knocking down GATA3 in primate embryos resulted in a failure to form trophectoderm. The discovery of the TEtra circuit indicates how trophectoderm commitment is regulated in human embryogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placenta / Diferenciación Celular / Células Madre Pluripotentes / Factor de Transcripción GATA2 / Factor de Transcripción GATA3 / Factor de Transcripción AP-2 Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placenta / Diferenciación Celular / Células Madre Pluripotentes / Factor de Transcripción GATA2 / Factor de Transcripción GATA3 / Factor de Transcripción AP-2 Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos