Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TET proteins regulate lineage specification and TCR-mediated expansion of iNKT cells (SMART-Seq)

ABSTRACT: TET proteins oxidize 5-methylcytosine to 5-hydroxymethylcytosine and further oxidation products in DNA. Here we report that simultaneous deletion of Tet2 and Tet3 in mouse double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T (iNKT) cells. Tet2-Tet3-double-deficient (DKO) iNKT cells displayed pronounced skewing towards the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in uncontrolled expansion dependent on the nonclassical MHC protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring proper development and maturation and suppressing aberrant T cell antigen receptor (TCR)-mediated proliferation.

ORGANISM(S): Mus musculus

PROVIDER: GSE85674 | GEO | 2016/11/21

SECONDARY ACCESSION(S): PRJNA339048

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TET proteins regulate lineage specification and TCR-mediated expansion of iNKT cells (CMS-Seq)

Project description:TET proteins oxidize 5-methylcytosine to 5-hydroxymethylcytosine and further oxidation products in DNA. Here we report that simultaneous deletion of Tet2 and Tet3 in mouse double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T (iNKT) cells. Tet2-Tet3-double-deficient (DKO) iNKT cells displayed pronounced skewing towards the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in uncontrolled expansion dependent on the nonclassical MHC protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring proper development and maturation and suppressing aberrant T cell antigen receptor (TCR)-mediated proliferation.

2016-11-21 | GSE66833 | GEO

TET proteins regulate lineage specification and TCR-mediated expansion of iNKT cells (RNA-Seq)

2016-11-21 | GSE66832 | GEO

TET proteins regulate lineage specification and TCR-mediated expansion of iNKT cells (ATAC-Seq)

2016-11-21 | GSE85743 | GEO

TET proteins regulate lineage specification and TCR-mediated expansion of iNKT cells (WGBS)

2016-11-21 | GSE72116 | GEO

TET proteins regulate Drosha expression and impact microRNAs in iNKT cells

Project description:DNA demethylases TET2 and TET3 play a fundamental role in thymic invariant natural killer T (iNKT) cell differentiation by mediating DNA demethylation of genes encoding for lineage specifying factors. Paradoxically, differential gene expression analysis revealed that significant number of genes were upregulated upon TET2 and TET3 loss in iNKT cells. This unexpected finding could be potentially explained if loss of TET proteins was reducing the expression of proteins that suppress gene expression. In this study, we discover that TET2 and TET3 synergistically regulate Drosha expression, by generating 5hmC across the gene body and by impacting chromatin accessibility. As Drosha is involved in microRNA biogenesis, we proceed to investigate the impact of TET2/3 loss on microRNAs in iNKT cells. We report that among the downregulated microRNAs are members of the Let7 family that downregulate in vivo the expression of the iNKT cell lineage specifying factor PLZF. Our data link TET proteins with microRNA expression and reveal an additional layer of TET mediated regulation of gene expression.

2024-08-30 | GSE267135 | GEO

Combined deficiency of Tet1 and Tet2 is compatible with development but leads to epigenetic instability

Project description:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 and Tet2 mediate 5hmC generation in mouse embryonic stem cells (ESCs) and various embryonic and adult tissues. To investigate the effects of combined deficiency of Tet1 and Tet2 on pluripotency and development, we have generated Tet1 and Tet2 double knockout (DKO) ESCs and mice. DKO ESCs were depleted of 5hmC, but remained pluripotent with subtle defects in differentiation and changes in gene expression. Double mutant embryos and chimeras exhibited mid-gestation defects and postnatal DKO mice displayed partially penetrant neonatal lethality and stochastic perturbation of imprinting. Viable DKO animals developed normally to adulthood but had reduced 5hmC level, increased 5mC level and lacked 5hmC in germ cells. Nevertheless, DKO mice of both sexes were fertile with females having smaller ovaries and reduced fertility. Our data suggest that both Tet1 and Tet2 contribute to 5hmC levels during development. Their combined loss does not block differentiation and embryogenesis, but leads to partially penetrant embryonic and perinatal abnormalities and compromised viability. Moreover, the presence of substantial levels of 5hmC in DKO embryos and adult mice suggests a significant contribution of Tet3 in hydroxylation of 5mC during development. Methylation patterns in tissue samples from a series of wt and Tet1/Tet2 DKO embryos, neonates and adults were generated using methylated DNA immunoprecipitation with antibodies against 5mC (MeDIP) and 5hmC (hMeDIP) followed by deep sequencing.

2013-02-01 | E-GEOD-42396 | biostudies-arrayexpress

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CUT&RUN]

Project description:TET proteins mediate DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and other oxidative derivatives. We have previously demonstrated a dynamic enrichment of 5hmC during T and invariant natural killer T cell lineage specification. Here, we investigate shared signatures in gene expression of Tet2/3 DKO CD4 single positive (SP) and iNKT cells in the thymus. We discover that TET proteins exert a fundamental role in regulating the expression of the lineage specifying factor Th-POK, which is encoded by Zbtb7b. We demonstrate that TET proteins mediate DNA demethylation - surrounding a proximal enhancer, critical for the intensity of Th-POK expression. In addition, TET proteins drive the DNA demethylation of site A at the Zbtb7b locus to facilitate GATA3 binding. GATA3 induces Th-POK expression in CD4 SP cells. Finally, by introducing a novel mouse model that lacks TET3 and expresses full length, catalytically inactive TET2, we establish a causal link between TET2 catalytic activity and lineage specification of both conventional and unconventional T cells.

2022-07-15 | GSE190228 | GEO

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [CATCH-SEQ]

2022-07-15 | GSE190227 | GEO

TET proteins regulate T cell and iNKT cell lineage specification in a TET2 catalytic dependent manner [RNA-Seq]

2022-07-15 | GSE190230 | GEO

Combined deficiency of Tet1 and Tet2 is compatible with development but leads to epigenetic instability

2013-02-01 | GSE42396 | GEO