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Zfp281 functions as a barrier in embryonic stem cells to extraembryonic endoderm stem cells differentiation.

ABSTRACT: Zfp281 functions as a barrier in embryonic stem cells to extraembryonic endoderm stem cells differentiation.

PROVIDER: PRJNA646194 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11497563_1.fastq.gz	Fastqsanger.gz
	SRR11497563_2.fastq.gz	Fastqsanger.gz
	SRR11497564_1.fastq.gz	Fastqsanger.gz
	SRR11497564_2.fastq.gz	Fastqsanger.gz
	SRR11497565_1.fastq.gz	Fastqsanger.gz

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Project description:Induction of the Arf tumor suppressor in response to hyperproliferative stress following oncogene activation activates a p53-dependent transcriptional program that limits the expansion of incipient cancer cells. Although Arf is not expressed in most tissues of fetal or young adult mice, it is physiologically expressed in the fetal yolk sac, a tissue derived from the extraembryonic endoderm. We demonstrate that expression of the mouse p19Arf protein marks late stages of extraembryonic endoderm differentiation in cultured embryoid bodies derived from either embryonic stem cells or induced pluripotent stem cells, and that Arf inactivation specifically delays the differentiation of the extraembryonic endoderm lineage, but not the formation of other germ cell lineages from pluripotent progenitors. Arf is required for the timely induction of extraembryonic endodermal cells in response to Ras/Erk signaling and, in turn, acts through p53 to ensure extraembryonic endoderm lineage development, but not maintenance. Remarkably, a significant temporal delay in extraembryonic endoderm differentiation detected during the maturation of Arf-null embryoid bodies is rescued by enforced expression of miR-205, a micro-RNA up-regulated by p19Arf and p53. Introduction of miR-205 into Arf-null embryonic stem cells rescues defective ExEn formation and elicits a program of gene expression that controls the migration and adhesion of embryonic endodermal cells. This occurs, at least in part, through atypical regulation of genes that control the epithelial-to-mesenchymal transition in cancer cells. Our findings suggest that noncanonical and canonical roles of Arf in extraembryonic endoderm development and tumor suppression, respectively, may be conceptually linked through mechanisms that govern cell-to-cell attachment and migration. 4 samples total two each at two time points in ESC development At each time point one sample was treted with miR-205 and the other with a GFP control vector

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Zfp281 functions as a barrier in embryonic stem cells to extraembryonic endoderm stem cells differentiation.

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