Ets2 is required for trophoblast stem cell self-renewal

Wen, Fang; Tynan, John A.; Ceceña, G; Williams, Roy; Múnera, Jorge O.; Mavrothalassitis, George; Oshima, Robert G.

doi:10.1016/j.ydbio.2007.09.024

Cited by 67 publications

(61 citation statements)

References 50 publications

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“…Ets transcription factor Mutants die by E8.5 with chorion absent and ectoplacental cone growth reduced and defective trophoblast stem cells self renewal (Yamamoto et al, 1998, Wen et al, 2007 (Zhang and Bradley, 1996) Acvr1b Activin/Nodal receptor 1B Mutants die by E9.5 with disorganized extraembryonic ectoderm (Gu et al, 1998) Acvr2, Acvr2b Activin/Nodal receptor 2 and 2B Compound homozygous mutants die by E8.5 (Song et al, 1999) …”

Section: Ets2mentioning

confidence: 99%

Development and function of trophoblast giant cells in the rodent placenta

Hu¹,

Cross²

2010

Int. J. Dev. Biol.

259

247

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Section: Ets2mentioning

confidence: 99%

Development and function of trophoblast giant cells in the rodent placenta

Hu¹,

Cross²

2010

Int. J. Dev. Biol.

259

247

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“…TS cells and ES cells both share the capacity to self-renew indefinitely in vitro in the presence of appropriate external signals and transcriptional machinery. ES cell self-renewal and pluripotency requires core transcription factors (TFs) POU5F1 (formerly known as OCT4), SOX2, and NANOG (Nichols et al 1998;Avilion et al 2003;Chambers et al 2003), while TS cell self-renewal and multipotency require TFs such as TCFAP2C, CDX2, EOMES, ESRRB, ETS2, SOX2, and TEAD4 (Chawengsaksophak et al 1997;Luo et al 1997;Russ et al 2000;Auman et al 2002;Avilion et al 2003;Wen et al 2007;Nishioka et al 2008). Recently, it has been shown that forced expression of Pou5f1, Sox2, Klf4, and Myc (formerly known as c-Myc) is sufficient to reprogram mouse and human fibroblasts into pluripotent cells (Takahashi et al 2007a,b;Wernig et al 2007).…”

mentioning

confidence: 99%

“…These factors have important roles in regulating TS cell self-renewal and placental development. TCFAP2C, SMARCA4, EOMES, ETS2, and GATA3 have been implicated in maintaining TS cell self-renewal and placental development (Ma et al 1997;Bultman et al 2000;Russ et al 2000;Auman et al 2002;Werling and Schorle 2002;Wen et al 2007;Kidder et al 2009). TCFAP2C is expressed in the TE of implantation stage embryos, and Tcfap2c-null embryos, which have reduced expression of CDX2 and EOMES, die around embryonic day (E) 8.5 (Werling and Schorle 2002).…”

mentioning

confidence: 99%

Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance

Kidder¹,

Palmer²

2010

Genome Res.

120

127

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Trophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (FGF4, INHBA/NODAL/TGFB1) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells, we used chromatin immunoprecipitation with DNA microarray hybridization (ChIP-chip) analysis to investigate targets of the TFs-TCFAP2C, EOMES, ETS2, and GATA3-and a chromatin remodeling factor, SMARCA4. We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell selfrenewal and pluripotency, co-occupancy of TCFAP2C, SMARCA4, and EOMES at a significant number of genes, and transcriptional regulatory circuitry within the five factors. Moreover, RNAi depletion of Tcfap2c, Smarca4, and Eomes transcripts resulted in a loss of normal colony morphology and down-regulation of TS cell-specific genes, suggesting an important role for TCFAP2C, SMARCA4, and EOMES in TS cell self-renewal. Through genome-wide mapping and global expression analysis of five TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.

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“…3d). Previous experiments using trophoblast stem (TS) cells, the in vitro equivalent of EXE, showed that Ets2 is required for TS cell self-renewal and for maintaining the expression of several genes including Bmp4, Cdx2, Eomes, Esrrb and Pace4 39,40 . The transcription factors Cdx2 and Elf5 are also required in TS cells for their self-renewal, with Cdx2 also maintaining Bmp4 expression 5,[41][42][43] .…”

Section: Article Nature Communications | Doi: 101038/ncomms2646mentioning

confidence: 99%

Ets2-dependent trophoblast signalling is required for gastrulation progression after primitive streak initiation

Polydorou

Georgiades

2013

Nat Commun

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Although extraembryonic ectoderm trophoblast signals the embryo for primitive streak initiation, a prerequisite for gastrulation, it is unknown whether it also signals for the progression of gastrulation after primitive streak initiation. Here, using Ets2 À / À mice, we show that trophoblast signalling is also required in vivo for primitive streak elongation, completion of intraembryonic mesoderm epithelial-mesenchymal transition and the development of anterior primitive streak derivatives such as the node. We show that Ets2-dependent trophoblast signalling is required for the maintenance of high levels of Nodal and Wnt3 expression in the epiblast and for the induction of Snail expression in the primitive streak, between embryonic day 6.3 and 6.7. Within extraembryonic ectoderm trophoblast, Ets2 maintains the expression of the transcription factors Elf5, Cdx2 and Eomes, and that of the signalling molecule Bmp4. We propose a model that provides a genetic explanation as to how Ets2 in trophoblast mediates the progression of gastrulation within the epiblast.

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Ets2 is required for trophoblast stem cell self-renewal

Cited by 67 publications

References 50 publications

Development and function of trophoblast giant cells in the rodent placenta

Development and function of trophoblast giant cells in the rodent placenta

Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance

Ets2-dependent trophoblast signalling is required for gastrulation progression after primitive streak initiation

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