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The combined action of Esrrb and Nr5a2 is essential for naïve pluripotency.

ABSTRACT: The combined action of Esrrb and Nr5a2 is essential for naïve pluripotency.

PROVIDER: PRJNA638601 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11974500_1.fastq.gz	Fastqsanger.gz
	SRR11974500_2.fastq.gz	Fastqsanger.gz
	SRR11974501_1.fastq.gz	Fastqsanger.gz
	SRR11974501_2.fastq.gz	Fastqsanger.gz
	SRR11974502_1.fastq.gz	Fastqsanger.gz

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The combined action of Esrrb and Nr5a2 is essential for naïve pluripotency.

Project description:The maintenance of pluripotency in mouse embryonic stem cells (ESCs) is governed by the action of an interconnected network of transcription factors. Among them, only Oct4 and Sox2 have been shown to be strictly required for the self-renewal of ESCs and pluripotency, particularly in culture conditions where differentiation cues are chemically inhibited. Here, we report that the conjunct activity of two orphan nuclear receptors, Esrrb and Nr5a2, parallels the importance of that of Oct4 and Sox2 in naïve ESCs. By occupying a large common set of regulatory elements, these two factors control the binding of Oct4, Sox2 and Nanog to DNA. Consequently, in their absence the pluripotency network collapses and the transcriptome is substantially deregulated, leading to the differentiation of ESCs. Altogether, this work identifies orphan nuclear receptors, previously thought to be performing supportive functions, as a new set of core regulators of naïve pluripotency.

2021-05-04 | GSE152186 | GEO

The combined action of Esrrb and Nr5a2 is essential for murine naive pluripotency.

Project description:The maintenance of pluripotency in mouse embryonic stem cells (ESCs) is governed by the action of an interconnected network of transcription factors. Among them, only Oct4 and Sox2 have been shown to be strictly required for the self-renewal of ESCs and pluripotency, particularly in culture conditions in which differentiation cues are chemically inhibited. Here, we report that the conjunct activity of two orphan nuclear receptors, Esrrb and Nr5a2, parallels the importance of that of Oct4 and Sox2 in naïve mouse ESCs. By occupying a large common set of regulatory elements, these two factors control the binding of Oct4, Sox2 and Nanog to DNA. Consequently, in their absence the pluripotency network collapses and the transcriptome is substantially deregulated, leading to the differentiation of ESCs. Altogether, this work identifies orphan nuclear receptors, previously thought to be performing supportive functions, as a set of core regulators of naïve pluripotency.

| S-EPMC8451941 | biostudies-literature

Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation [Microarray]

Project description:Self-renewal of embryonic stem cells (ESCs) cultured in serum-LIF is incomplete with some cells initiating differentiation. While this is reflected in heterogeneous expression of naive pluripotency transcription factors (TFs), the link between TF heterogeneity and differentiation is not fully understood. Here we purify ESCs with distinct TF expression levels from serum-LIF cultures to uncover early events during commitment from naïve pluripotency. ESCs carrying fluorescent Nanog and Esrrb reporters show Esrrb downregulation only in NANOGlow cells. Independent Esrrb reporter lines demonstrate that ESRRBnegative ESCs cannot effectively self-renew. Upon ESRRB loss, pre-implantation pluripotency gene expression collapses. ChIP-Seq identifies different regulatory element classes that bind both OCT4 and NANOG in ESRRBhigh cells. Class I elements lose NANOG and OCT4 binding in ESRRBnegative ESCs and associate with genes expressed preferentially in naïve ESCs. In contrast, class II elements retain OCT4 but not NANOG binding in ESRRBnegative cells and associate with more broadly expressed genes. Therefore, mechanistic differences in TF function act cumulatively to restrict potency during exit from naïve pluripotency.

2018-09-13 | GSE118906 | GEO

Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation [ChIP-seq]

2018-09-13 | GSE118905 | GEO

‘Naïve’ ESRRB+ iPSCs with the capacity for rapid neural differentiation

Project description:Several groups have reported the existence of a form of pluripotency that resembles that of mouse embryonic stem cells (mESCs), i.e., a naïve state, in human pluripotent stem cells; however, the characteristics vary between reports. The nuclear receptor ESRRB is expressed in mESCs and plays a significant role in their self-renewal, but its expression has not been observed in most naïve-like human induced pluripotent stem cells (hiPSCs). In this study, we modified several methods for converting hiPSCs into a naïve state through the transgenic expression of several reprogramming factors. The resulting cells express the components of the core transcriptional network of mESCs, including ESRRB, at high levels, which suggests the existence of naïve-state hiPSCs that are similar to mESCs. We also demonstrate that these cells differentiate more readily into neural cells than do conventional hiPSCs. These features may be beneficial for their use in disease modeling and regenerative medicine.

2017-11-20 | GSE104583 | GEO

Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.

Project description:Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.

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Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation [Microarray]

Project description:Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation [Microarray]

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Mitotic bookmarking redundancy by nuclear receptors mediates robust post-mitotic reactivation of the pluripotency network.

Project description:Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the significance and importance of their bookmarking function. Here, we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover an unexpected redundancy among members of the protein superfamily of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ESRRB is essential in maintaining pluripotency in mouse embryonic stem cells, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly the most rapidly and strongly reactivated ones. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.

2023-11-20 | PXD038950 | Pride

‘Naïve’ ESRRB+ iPSCs with the capacity for rapid neural differentiation

Project description:‘Naïve’ ESRRB+ iPSCs with the capacity for rapid neural differentiation

| PRJNA413135 | ENA

Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation [ChIP-seq]

Project description:Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation [ChIP-seq]

| PRJNA487261 | ENA