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

被引：121

作者：

Krendl, Christian ^{[1
]}

Shaposhnikov, Dmitry ^{[1
]}

Rishko, Valentyna ^{[1
]}

Ori, Chaido ^{[1
]}

Ziegenhain, Christoph ^{[2
]}

Sass, Steffen ^{[3
]}

Simon, Lukas ^{[3
]}

Mueller, Nikola S. ^{[3
]}

Straub, Tobias ^{[4
]}

Brooks, Kelsey E. ^{[5
]}

Chavez, Shawn L. ^{[5
]}

Enard, Wolfgang ^{[2
]}

Theis, Fabian J. ^{[3
,6
]}

Drukker, Micha ^{[1
]}

机构：

[1] Helmholtz Ctr Munich, Inst Stem Cell Res, D-85764 Neuherberg, Germany

[2] Ludwig Maximilians Univ Munchen, Dept Biol 2, Anthropol & Human Genom, D-82152 Martinsried, Germany

[3] Helmholtz Ctr Munich, Inst Computat Biol, D-85764 Neuherberg, Germany

[4] Ludwig Maximilians Univ Munchen, Core Facil Bioinformat, Biomed Ctr, D-82152 Martinsried, Germany

[5] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod & Dev Sci, Beaverton, OR 97006 USA

[6] Tech Univ Munich, Dept Math, D-85748 Garching, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2017年 / 114卷 / 45期

关键词：

trophectoderm; trophoblast; BMP4; hESC; differentiation; BONE MORPHOGENETIC PROTEIN-4; TROPHOBLAST DIFFERENTIATION; FACTOR AP-2-GAMMA; GENE; MOUSE; EXPRESSION; LINEAGE; PREIMPLANTATION; TEAD4; CDX2;

D O I：

10.1073/pnas.1708341114

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：E9579 / E9588

页数：10

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