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Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells [ATAC-seq, ChIP-seq, RNA-seq, CUT&Tag]

ABSTRACT: Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells [ATAC-seq, ChIP-seq, RNA-seq, CUT&Tag]

PROVIDER: PRJNA669873 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12842427_1.fastq.gz	Fastqsanger.gz
	SRR12842427_2.fastq.gz	Fastqsanger.gz
	SRR12842428_1.fastq.gz	Fastqsanger.gz
	SRR12842428_2.fastq.gz	Fastqsanger.gz
	SRR12842429_1.fastq.gz	Fastqsanger.gz

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Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells [ATAC-seq, ChIP-seq, RNA-seq, CUT&Tag]

Project description:The 3D genome organization is crucial for gene regulation. Although recent studies have revealed a uniquely relaxed genome conformation in totipotent early blastomeres of both fertilized and cloned embryos, how weakened higher-order chromatin structure is functionally linked to totipotency acquisition remains elusive. Using low-input Hi-C, ATAC-seq, and ChIP-seq, we systematically examined the dynamics of 3D genome and epigenome during pluripotent to totipotent-like state transition in mouse embryonic stem cells (ESCs). The spontaneously converted 2-cell-embryo-like cells (2CLCs) exhibited more relaxed chromatin architecture compared to ESCs, including global weakening of both enhancer-promoter interactions and TAD insulation. While the former correlated with inactivation of ESC enhancers and down-regulation of pluripotent genes, the latter might facilitate contacts between the putative new enhancers arising in 2CLCs and neighboring 2C genes. Importantly, disruption of chromatin organization by depleting CTCF or the cohesin complex promoted the ESC to 2CLC transition. Our results thus establish a critical role of 3D genome organization in totipotency acquisition.

2021-10-20 | GSE159621 | GEO

Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells

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Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells [Hi-C]

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Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells

Project description:Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells

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Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells [Hi-C]

Project description:Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells [Hi-C]

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Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [CUT&Tag]

Project description:Totipotent cells have more robust developmental potency than any other cell types, giving rise to both embryonic and extraembryonic tissues. Stable totipotent cultures and deciphering the principles of totipotency regulation would be invaluable to understand cell plasticity and lineage segregation in early development. Our approach of remodeling the pericentromeric heterochromatin and re-establishing the totipotency-specific broad H3K4me3 domains promotes the pluri-to-totipotency transition. Our protocol establishes a closer match of mouse 2-cell (2C) embryos than any other 2C-like cells. These totipotent-like stem cells (TLSCs) are stable in culture and possess unique molecular features of the mouse 2C embryo. Functionally, TLSCs are competent for germline transmission and give rise to both embryonic and extraembryonic lineages at high frequency. Therefore, TLSCs represent a highly valuable cell type for studies of totipotency and embryology.

2022-02-11 | GSE166210 | GEO

Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [CUT&Tag 2]

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Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [CUT&Tag]

Project description:Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [CUT&Tag]

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Relaxed 3D genome conformation facilitates the pluripotent to totipotent-like state transition in embryonic stem cells.

Project description:The 3D genome organization is crucial for gene regulation. Although recent studies have revealed a uniquely relaxed genome conformation in totipotent early blastomeres of both fertilized and cloned embryos, how weakened higher-order chromatin structure is functionally linked to totipotency acquisition remains elusive. Using low-input Hi-C, ATAC-seq and ChIP-seq, we systematically examined the dynamics of 3D genome and epigenome during pluripotent to totipotent-like state transition in mouse embryonic stem cells (ESCs). The spontaneously converted 2-cell-embryo-like cells (2CLCs) exhibited more relaxed chromatin architecture compared to ESCs, including global weakening of both enhancer-promoter interactions and TAD insulation. While the former correlated with inactivation of ESC enhancers and down-regulation of pluripotent genes, the latter might facilitate contacts between the putative new enhancers arising in 2CLCs and neighboring 2C genes. Importantly, disruption of chromatin organization by depleting CTCF or the cohesin complex promoted the ESC to 2CLC transition. Our results thus establish a critical role of 3D genome organization in totipotency acquisition.

| S-EPMC8643704 | biostudies-literature

Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cell [RNA-Seq]

Project description:Totipotency is defined as the ability of a cell to generate all the cell types of an organism, including those of the extraembryonic tissues. Unlike pluripotency, the molecular features and the establishment of totipotency are poorly understood. In mouse embryonic stem cell (ESC) culture, a small percentage of cells transits into a totipotent state by expressing a group of genes that are only expressed in 2-cell-stage embryos. To understand how this transition takes place, we performed single cell RNA-seq analysis which revealed a two-step transcriptional reprogramming process characterized by downregulation of pluripotent genes in the first step and upregulation of the 2-cell embryo-specific genes in the second step. To identify factors controlling the transition process, we performed a CRISPR/Cas9-mediated genetic screen which revealed Myc and Dnmt1 as two factors preventing the transition. Mechanistic studies demonstrate that Myc prevents down-regulation of the genes in the first step, while Dnmt1 impedes gene activation in the second step. Collectively, our study reveals insights into the mechanism underlying establishment and regulation of totipotent state in ESCs.

2019-04-12 | GSE121451 | GEO

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