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Role of TET3 in mouse embryonic and adult hematopoiesis [RNA-Seq]

ABSTRACT: Role of TET3 in mouse embryonic and adult hematopoiesis [RNA-Seq]

PROVIDER: PRJNA1190067 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31480559_1.fastq.gz	Fastqsanger.gz
	SRR31480559_2.fastq.gz	Fastqsanger.gz
	SRR31480560_1.fastq.gz	Fastqsanger.gz
	SRR31480560_2.fastq.gz	Fastqsanger.gz
	SRR31480561_1.fastq.gz	Fastqsanger.gz

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Role of TET3 in mouse embryonic and adult hematopoiesis

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TET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn

Project description:Ten-eleven-translocation (TET) proteins catalyze DNA hydroxylation, playing an important role in demethylation of DNA in mammals. Remarkably, although hydroxymethylation levels are high in the mouse brain, the potential role of TET proteins in adult neurogenesis is unknown. We show here that a non-catalytic action of TET3 is essentially required for the maintenance of the neural stem cell (NSC) pool in the adult subventricular zone (SVZ) niche by preventing premature differentiation of NSCs into non-neurogenic astrocytes. This occurs through direct binding of TET3 to the paternal transcribed allele of the imprinted gene Small nuclear ribonucleoprotein-associated polypeptide N (Snrpn), contributing to transcriptional repression of the gene. The study also identifies BMP2 as an effector of the astrocytic terminal differentiation mediated by SNRPN. Our work describes a novel mechanism of control of an imprinted gene in the regulation of adult neurogenesis through an unconventional role of TET3.

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Project description:TET3 is a member of the Ten-eleven translocation (TET) family of enzymes which oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Tet3 is highly expressed in the brain, where 5hmC levels are most abundant. In adult mice, we observed that TET3 is present in mature neurons and oligodendrocytes but is absent in astrocytes. To investigate the function of TET3 in adult post-mitotic neurons, we crossed Tet3 floxed mice with a neuronal Cre-expressing mouse line, Camk2a-CreERT2, obtaining a Tet3 conditional KO mouse line. Ablation of Tet3 in adult mature neurons resulted in increased anxiety-like behavior with concomitant hypercorticalism, and impaired hippocampal-dependent spatial orientation. Transcriptome and gene-specific expression analysis of the hippocampus showed dysregulation of genes involved in glucocorticoid signaling pathway (HPA axis) in the ventral hippocampus, whereas upregulation of immediate early genes (IEGs) was observed in both dorsal and ventral hippocampal areas. Additionally, Tet3 cKO mice exhibit increased dendritic spine maturation in the ventral CA1 hippocampal subregion. Based on these observations, we suggest that TET3 is involved in molecular alterations, that govern hippocampal-dependent functions. These results reveal a critical role for epigenetic modifications in modulating brain functions, opening new insights into the molecular basis of psychiatric disorders.

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