Cargando…
GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency
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 AP...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5692555/ https://www.ncbi.nlm.nih.gov/pubmed/29078328 http://dx.doi.org/10.1073/pnas.1708341114 |
_version_ | 1783279905218232320 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Krendl, Christian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5692555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-56925552017-11-20 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 Proc Natl Acad Sci U S A PNAS Plus 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. National Academy of Sciences 2017-11-07 2017-10-25 /pmc/articles/PMC5692555/ /pubmed/29078328 http://dx.doi.org/10.1073/pnas.1708341114 Text en Copyright © 2017 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | PNAS Plus 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 GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency |
title | GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency |
title_full | GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency |
title_fullStr | GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency |
title_full_unstemmed | GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency |
title_short | GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency |
title_sort | gata2/3-tfap2a/c transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5692555/ https://www.ncbi.nlm.nih.gov/pubmed/29078328 http://dx.doi.org/10.1073/pnas.1708341114 |
work_keys_str_mv | AT krendlchristian gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT shaposhnikovdmitry gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT rishkovalentyna gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT orichaido gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT ziegenhainchristoph gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT sasssteffen gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT simonlukas gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT mullernikolas gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT straubtobias gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT brookskelseye gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT chavezshawnl gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT enardwolfgang gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT theisfabianj gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency AT drukkermicha gata23tfap2actranscriptionfactornetworkcoupleshumanpluripotentstemcelldifferentiationtotrophectodermwithrepressionofpluripotency |