GATA2/3-TFAP2A/C Transcription Factor Network Couples Human Pluripotent Stem Cell Differentiation to Trophectoderm with Repression of Pluripotency

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2017 Oct 29

PMID 29078328

Citations 96

Authors

Christian Krendl

Dmitry Shaposhnikov

Valentyna Rishko

Chaido Ori

Christoph Ziegenhain

Steffen Sass

Lukas Simon

Nikola S Muller

Tobias Straub

Kelsey E Brooks

Shawn L Chavez

Wolfgang Enard

Fabian J Theis

Micha Drukker

Affiliations

Soon will be listed here.

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 Functional manipulation of and indicated that they directly couple trophoblast-specific gene induction with suppression of pluripotency. In accordance, knocking down 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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References

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

Wei G, Abraham B, Yagi R, Jothi R, Cui K, Sharma S . Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity. 2011; 35(2):299-311. PMC: 3169184. DOI: 10.1016/j.immuni.2011.08.007. View

Blakeley P, Fogarty N, Del Valle I, Wamaitha S, Hu T, Elder K . Defining the three cell lineages of the human blastocyst by single-cell RNA-seq. Development. 2015; 142(20):3613. PMC: 4631772. DOI: 10.1242/dev.131235. View

Drukker M, Tang C, Ardehali R, Rinkevich Y, Seita J, Lee A . Isolation of primitive endoderm, mesoderm, vascular endothelial and trophoblast progenitors from human pluripotent stem cells. Nat Biotechnol. 2012; 30(6):531-42. PMC: 3672406. DOI: 10.1038/nbt.2239. View

Niakan K, Eggan K . Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. Dev Biol. 2012; 375(1):54-64. DOI: 10.1016/j.ydbio.2012.12.008. View

Xie W, Schultz M, Lister R, Hou Z, Rajagopal N, Ray P . Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell. 2013; 153(5):1134-48. PMC: 3786220. DOI: 10.1016/j.cell.2013.04.022. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Nishioka N, Inoue K, Adachi K, Kiyonari H, Ota M, Ralston A . The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell. 2009; 16(3):398-410. DOI: 10.1016/j.devcel.2009.02.003. View

Hinman V, Davidson E . Evolutionary plasticity of developmental gene regulatory network architecture. Proc Natl Acad Sci U S A. 2007; 104(49):19404-9. PMC: 2148302. DOI: 10.1073/pnas.0709994104. View

10.

Donnison M, Beaton A, Davey H, Broadhurst R, LHuillier P, Pfeffer P . Loss of the extraembryonic ectoderm in Elf5 mutants leads to defects in embryonic patterning. Development. 2005; 132(10):2299-308. DOI: 10.1242/dev.01819. View

11.

Anson-Cartwright L, Dawson K, Holmyard D, Fisher S, Lazzarini R, CROSS J . The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta. Nat Genet. 2000; 25(3):311-4. DOI: 10.1038/77076. View

12.

Benchetrit H, Herman S, van Wietmarschen N, Wu T, Makedonski K, Maoz N . Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells. Cell Stem Cell. 2015; 17(5):543-56. DOI: 10.1016/j.stem.2015.08.006. View

13.

Renaud G, Stenzel U, Maricic T, Wiebe V, Kelso J . deML: robust demultiplexing of Illumina sequences using a likelihood-based approach. Bioinformatics. 2014; 31(5):770-2. PMC: 4341068. DOI: 10.1093/bioinformatics/btu719. View

14.

Ray S, Dutta D, Rumi M, Kent L, Soares M, Paul S . Context-dependent function of regulatory elements and a switch in chromatin occupancy between GATA3 and GATA2 regulate Gata2 transcription during trophoblast differentiation. J Biol Chem. 2008; 284(8):4978-88. PMC: 2643515. DOI: 10.1074/jbc.M807329200. View

15.

Trapnell C, Pachter L, Salzberg S . TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009; 25(9):1105-11. PMC: 2672628. DOI: 10.1093/bioinformatics/btp120. View

16.

Kent W, Sugnet C, Furey T, Roskin K, Pringle T, Zahler A . The human genome browser at UCSC. Genome Res. 2002; 12(6):996-1006. PMC: 186604. DOI: 10.1101/gr.229102. View

17.

Law C, Chen Y, Shi W, Smyth G . voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014; 15(2):R29. PMC: 4053721. DOI: 10.1186/gb-2014-15-2-r29. View

18.

Ziegenhain C, Vieth B, Parekh S, Reinius B, Guillaumet-Adkins A, Smets M . Comparative Analysis of Single-Cell RNA Sequencing Methods. Mol Cell. 2017; 65(4):631-643.e4. DOI: 10.1016/j.molcel.2017.01.023. View

19.

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

20.

Cao Z, Carey T, Ganguly A, Wilson C, Paul S, Knott J . Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage. Development. 2015; 142(9):1606-15. PMC: 4419278. DOI: 10.1242/dev.120238. View