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Esrrb function in the extraembryonic ectoderm is required for proper primordial germ cell specification [ChIP-seq]

ABSTRACT: Estrogen related receptor beta (Esrrb) is an orphan nuclear receptor that is required for self-renewal and pluripotency in mouse embryonic stem (ES) cells. However, in the early post-implantation mouse embryo, Esrrb is specifically expressed in the extraembryonic ectoderm (ExE) and plays a crucial role in trophoblast development. In this study, to better understand the function of Esrrb in trophoblast lineage cells, we performed microarray analysis of Esrrb-null mutant versus wild-type mouse embryos. To further characterize the regulatory targets of Esrrb, we treated trophoblast stem (TS) cells with either Esrrb inhibitor DES or vehicle and compared their global gene expression profile via RNA-seq analysis. In addition, to ask whether these target genes are directly regulated by Esrrb, we performed Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis of TS cells using anti-Esrrb antibody.

ORGANISM(S): Mus musculus

PROVIDER: GSE123361 | GEO | 2019/07/15

REPOSITORIES: GEO

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Esrrb function in the extraembryonic ectoderm is required for proper primordial germ cell specification [microarray]

Project description:Estrogen related receptor beta (Esrrb) is an orphan nuclear receptor that is required for self-renewal and pluripotency in mouse embryonic stem (ES) cells. However, in the early post-implantation mouse embryo, Esrrb is specifically expressed in the extraembryonic ectoderm (ExE) and plays a crucial role in trophoblast development. In this study, to better understand the function of Esrrb in trophoblast lineage cells, we performed microarray analysis of Esrrb-null mutant versus wild-type mouse embryos. To further characterize the regulatory targets of Esrrb, we treated trophoblast stem (TS) cells with either Esrrb inhibitor DES or vehicle and compared their global gene expression profile via RNA-seq analysis. In addition, to ask whether these target genes are directly regulated by Esrrb, we performed Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis of TS cells using anti-Esrrb antibody.

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Esrrb function in the extraembryonic ectoderm is required for proper primordial germ cell specification [RNA-seq]

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Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of Trophoblast Stem Cells

Project description:Derivation and maintenance of TS cells depends on the presence of Fgf signalling. Numerous gene knock-out experiments identified the mitogen activated kinase Mek/Erk branch of the Fgf signalling pathway as predominantly active in both TS cells and extraembryonic ectoderm. Therefore, we tested changes in expression of the key TS cell transcription factors (TFs) upon Mek/Erk inhibition using the Mek inhibitor PD0325901 (“PD03”). To obtain an unbiased genome-wide coverage of the immediate-early response genes of Mek inhibition in TS cells, we performed RNA-seq analysis after 3h and 24h of PD03 treatment. Notably, of the known TS cell TFs, this analysis confirmed Esrrb as the earliest, most rapidly silenced gene upon PD03 treatment. In order to gain first insights into which genes may be primary targets of Esrrb, we treated TS cells with the synthetic nonsteroidal estrogen diethylstilbestrol (DES), an estrogen-related receptor (Err) antagonist and also performed RNA-seq upon short (24h) and prolonged (4d) DES treatment. Finally, to obtain a comprehensive global overview of the binding sites of Esrrb in TS cells, and of its interaction with Lsd1 and Nr0b1 (Dax1), we performed chromatin immunoprecipitation (ChIP)-seq experiments on these factors.

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Esrrb function in the extraembryonic ectoderm is required for proper primordial germ cell specification [microarray]

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