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

Krendl C, Shaposhnikov D, Rishko V, Ori C, Ziegenhain C, Sass S, Simon L, Mueller NS, Straub T, Brooks KE, Chavez SL, Enard W, Theis FJ, Drukker M (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 114

Pages Range: E9579-E9588

Journal Issue: 45

DOI: 10.1073/pnas.1708341114

Abstract

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.

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Oregon Health and Science University (OSHU) US United States (USA) (US)

How to cite

APA:

Krendl, C., Shaposhnikov, D., Rishko, V., Ori, C., Ziegenhain, C., Sass, S.,... Drukker, M. (2017). GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency. Proceedings of the National Academy of Sciences of the United States of America, 114(45), E9579-E9588. https://doi.org/10.1073/pnas.1708341114

MLA:

Krendl, Christian, et al. "GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency." Proceedings of the National Academy of Sciences of the United States of America 114.45 (2017): E9579-E9588.

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