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Krendl, C. ; Shaposhnikov, D. ; Rishko, V. ; Ori, C. ; Ziegenhain, C.* ; Sass, S. ; Simon, L. ; Müller, N.S. ; Straub, T.* ; Brooks, K.E.* ; Chavez, S.L.* ; Enard, W.* ; Theis, F.J. ; Drukker, M.

GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency.

Proc. Natl. Acad. Sci. U.S.A. 114, E9579-E9588 (2017)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Bmp4 ; Differentiation ; Hesc ; Trophectoderm ; Trophoblast; Bone Morphogenetic Protein-4; Gene-expression Data; Trophoblast Differentiation; In-vitro; Mammalian Development; Mesoderm Formation; Factor Ap-2-gamma; Mouse Embryos; Rna-seq; Lineage
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 114, Heft: 45, Seiten: E9579-E9588 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Verlagsort Washington
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
Institute of Computational Biology (ICB)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Stem Cell and Neuroscience
Enabling and Novel Technologies
PSP-Element(e) G-552400-001
G-503800-001
PubMed ID 29078328
DOI 10.1073/pnas.1708341114
WOS ID WOS:000414631200020
Scopus ID 85033451046
Erfassungsdatum 2017-10-30
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