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

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

PROVIDER: PRJNA413135 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6130240.fastq.gz	Fastqsanger.gz
	SRR6130241.fastq.gz	Fastqsanger.gz
	SRR6130236.fastq.gz	Fastqsanger.gz
	SRR6130237.fastq.gz	Fastqsanger.gz
	SRR6130238.fastq.gz	Fastqsanger.gz

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‘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

Naive-like 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 naive 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 naive-like human induced pluripotent stem cells (hiPSCs). In this study, we modified several methods for converting hiPSCs into a naive 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 naive-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.

| S-EPMC5785673 | biostudies-other

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

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

ESRRB Facilitates the Conversion of Trophoblast-like Stem Cells from Induced Pluripotent Stem cells by Directly Regulating KRT8 and CDX2

Project description:Porcine induced pluripotent stem cells (piPSCs) could serve as a great model system for human stem cell pre-clinical research. However, the pluripotency gene network of piPSCs, especially the function for the core transcription factor ESRRB, was poorly understood. Here, we constructed ESRRB-overexpressing piPSCs (ESRRB-piPSCs). Compared with the control piPSCs (CON-piPSCs), the ESRRB-piPSCs showed flat, monolayered colony morphology. Moreover, the ESRRB-piPSCs showed greater chimeric capacity into trophectoderm than CON-piPSCs. We found that ESRRB could directly regulate the expressions of trophoblast stem cell (TSC)-specific markers, including KRT8, KRT18 and CDX2, through binding to their promoter regions. Mutational analysis proved that the N-terminus zinc finger domain is indispensable for ESRRB to regulate the TSC markers. Furthermore, this regulation needs the participation of OCT4. Accordingly, the cooperation between ESRRB and OCT4 facilitates the conversion from pluripotent state to the trophoblast-like state.

2022-02-17 | PXD027539 | Pride

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

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

| PRJNA638601 | ENA

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.

| PRJNA487255 | ENA

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]

| PRJNA487260 | ENA

Genome-wide maps of ESRRB binding in pluripotent (2iL) and differentiated (48h, 96h) mES cells

Project description:We report the application of sequencing technology for profiling of genome-wide ESRRB binding in mouse ES cells. We generated genome-wide chromatin-state maps of mouse embryonic stem cells maintained in pluripotent state (2iL) and differentiated for 48 and 96 hours (48 and 96). We find that the large majority of ESRRB binding occurs in 2iL and at 48 hours and that several formative genes promoters are bound by ESRRB in 2iL and at 48h. Moreover ESRRB peaks on naïve genes (e.g. Tfcp2l1, Nanog) decrease as soon as cells start differentiating while peaks on formative genes are present in 2iL and the signal is maintained (or increased) at 48 hours, further endorsing the concept of Esrrb as a direct activator of the formative gene program during the Reversible phase.

2023-01-25 | GSE184131 | GEO

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