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Medientyp:
E-Artikel
Titel:
GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency
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
Entstehung:
Anmerkungen:
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>