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Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cell

ABSTRACT: Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cell

PROVIDER: PRJNA497377 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8074410.fastq.gz	Fastqsanger.gz
	SRR8074420.fastq.gz	Fastqsanger.gz
	SRR8074440_1.fastq.gz	Fastqsanger.gz
	SRR8074440_2.fastq.gz	Fastqsanger.gz
	SRR8074450.fastq.gz	Fastqsanger.gz

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

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.

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Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cell [CRISPR-Cas9 screen]

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Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cells.

Project description:Totipotency refers to the ability of a cell to generate all of the cell types of an organism. Unlike pluripotency, the establishment of totipotency is poorly understood. In mouse embryonic stem cells, Dux drives a small percentage of cells into a totipotent state by expressing 2-cell-embryo-specific transcripts. To understand how this transition takes place, we performed single-cell RNA-seq, 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 elements in the second step. To identify factors controlling the transition, we performed a CRISPR-Cas9-mediated screen, which revealed Myc and Dnmt1 as two factors preventing the transition. Mechanistic studies demonstrate that Myc prevents downregulation of pluripotent genes in the first step, while Dnmt1 impedes 2-cell-embryo-specific gene activation in the second step. Collectively, the findings of our study reveal insights into the establishment and regulation of the totipotent state in mouse embryonic stem cells.

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Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cell

Project description:This SuperSeries is composed of the SubSeries listed below.

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