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Global transcriptional analysis of human extended pluripotent stem cells, human primed pluripotent stem cells, mouse extended pluripotent stem cells, and mouse embryonic stem cells by RNA-seq

ABSTRACT: Global transcriptional analysis of human extended pluripotent stem cells, human primed pluripotent stem cells, mouse extended pluripotent stem cells, and mouse embryonic stem cells by RNA-seq

OTHER RELATED OMICS DATASETS IN: GSE80732GSE89303GSE89301

PROVIDER: PRJNA319819 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3458020.fastq.gz	Fastqsanger.gz
	SRR3458030_1.fastq.gz	Fastqsanger.gz
	SRR3458030_2.fastq.gz	Fastqsanger.gz
	SRR3458021.fastq.gz	Fastqsanger.gz
	SRR3458022.fastq.gz	Fastqsanger.gz

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Project description:All mammals develop from embryonic founder cells with the ability to generate all of the differentiated cells that constitute the organism. Capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology. Here, we show that a chemical cocktail enables the derivation of a new stem cell type from both mice and humans, designated as extended pluripotent stem (EPS) cells. A single human or mouse EPS cell is able to contribute to both embryonic and extraembryonic lineages in inter- and intra-species chimeric mouse conceptuses respectively. Compared to known pluripotent stem cells, EPS cells show upregulation of gene modules marking embryonic cells from early preimplantation development. Further analysis shows that PARP1 inhibition is required for maintaining EPS potency. Our findings constitute a first step towards capturing authentic mammalian totipotency in vitro, and open new avenues for basic and translational research.

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Project description:Among all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their unrestricted developmental potential, able to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic (ExEm) tissues, in particular, those giving rise to the placenta in vivo. To date, it remains unknown whether stem cells with both embryonic and extraembryonic developmental potency can be captured and maintained in vitro. Here, we identify a new chemical cocktail that allows for the generation of stem cells with extended developmental potency from mouse and human, designated as extended pluripotent stem (EPS) cells, which is capable of chimerizing both embryonic and extraembryonic tissues. Importantly, a single mouse EPS (mEPS) cell shows widespread contribution to both embryonic and extraembryonic lineages in chimeric mouse conceptuses at late-gestation stages, and permits generation of high-grade germline competent chimeras as well as single EPS-derived viable mice by tetraploid complementation. Furthermore, human EPS (hEPS) cells contribute to embryonic and extraembryonic tissues in interspecies chimeric mouse conceptuses. Compared to known PSCs, EPS cells show unique gene modules that upregulate in embryonic cells from early preimplantation development. Further analysis shows that PARP1 inhibition is required for maintaining EPS potency. Our findings constitute a first step towards capturing pluripotent stem cells with extraembryonic developmental potentials in culture, and open new avenues for generating mammalian PSCs with robust chimeric competency for basic and translational research.

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