Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE279236 | GEO | 2024/11/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability

Project description:TET proteins are tumor suppressors that through their catalytic activity oxidize 5-methylcytosine to 5-hydroxymethylcytosine, to promote DNA demethylation and to regulate gene expression. Notably, TET2 is the second most frequently mutated gene in hematological malignancies, including T cell lymphomas. However, murine models with deletion of TET2 do not exhibit T cell expansion, presumably due to redundancy with other members of the TET family of proteins. In order to gain insight on the TET mediated molecular events that safeguard T cells from aberrant proliferation we performed serial adoptive transfers of murine CD4 T cells that lack concomitantly TET2 and TET3 to fully immunocompetent congenic mice. Our data reveal a progressive acquisition of malignant traits upon loss of TET2 and TET3 that is characterized by loss of genomic integrity, acquisition of aneuploidy and upregulation of the protooncogene Myc.

2024-11-11 | GSE278239 | GEO

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability [WGS]

Project description:TET proteins are tumor suppressors that through their catalytic activity oxidize 5-methylcytosine to 5-hydroxymethylcytosine, to promote DNA demethylation and to regulate gene expression. Notably, TET2 is one of the most frequently mutated genes in hematological malignancies, including T cell lymphomas. However, murine models with deletion of TET2 do not exhibit T cell expansion, presumably due to redundancy with other members of the TET family of proteins. In order to gain insight on the TET mediated molecular events that safeguard T cells from aberrant proliferation we performed serial adoptive transfers of murine CD4 T cells that lack concomitantly TET2 and TET3 to fully immunocompetent congenic mice. Our data reveal a progressive acquisition of malignant traits upon loss of TET2 and TET3 that is characterized by loss of genomic integrity, acquisition of aneuploidy and upregulation of the protooncogene Myc.

2024-11-07 | GSE276581 | GEO

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability [BGI-RNA-Seq]

Project description:TET proteins mediate DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and other oxidative derivatives. While we have previously demonstrated a dynamic enrichment of 5hmC during T cell lineage specification, the impact of TET proteins in CD4 cell lineage differentiation remains largely unknown. Here, we discover that TET proteins exert a fundamental role in regulating the differentiation and maturation of the CD4 lineage by controlling the expression of the lineage specifying factor Th-POK, which is encoded by Zbtb7b. We demonstrate that TET proteins mediate DNA demethylation of a proximal enhancer, critical for the stability of Th-POK expression. In addition, TET proteins drive the DNA demethylation of site A at the Zbtb7b locus to facilitate GATA3 binding, an event critical for Th-POK expression and subsequent CD4 maturation. The impaired maturation of Tet2/3 DKO CD4 cells leads to the acquisition of a stemness signature and results in acquisition of malignant traits.

2024-11-07 | GSE190226 | GEO

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability

Project description:Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability

| PRJNA1166157 | ENA

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability

Project description:Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability

| PRJNA1171448 | ENA

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability [WGS]

Project description:Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability [WGS]

| PRJNA1157871 | ENA

Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability [BGI-RNA-Seq]

Project description:Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability [BGI-RNA-Seq]

| PRJNA786484 | ENA

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis

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

2023-05-22 | GSE200230 | GEO

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis.

Project description:TET2/3 play a well-known role in epigenetic regulation and mouse development. However, their function in cellular differentiation and tissue homeostasis remains poorly understood. Here we show that ablation of TET2/3 in intestinal epithelial cells results in a murine phenotype characterized by a severe homeostasis imbalance in the small intestine. Tet2/3-deleted mice show a pronounced loss of mature Paneth cells as well as fewer Tuft and more Enteroendocrine cells. Further results show major changes in DNA methylation at putative enhancers, which are associated with cell fate-determining transcription factors and functional effector genes. Notably, pharmacological inhibition of DNA methylation partially rescues the methylation and cellular defects. TET2/3 loss also alters the microbiome, predisposing the intestine to inflammation under homeostatic conditions and acute inflammation-induced death. Together, our results uncover previously unrecognized critical roles for DNA demethylation, possibly occurring subsequently to chromatin opening during intestinal development, culminating in the establishment of normal intestinal crypts.

| S-EPMC10326054 | biostudies-literature

Loss of TET2 and TET3 in regulatory T cells unleashes effector function.

Project description:TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3fl/flFoxp3Cre mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these mice show altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. In littermate mice with severe inflammation, both CD4+Foxp3+ and CD4+Foxp3- cells show strong skewing towards Tfh/Th17 phenotypes. Wild-type Treg cells in mixed bone marrow chimeras and in Tet2/3fl/flFoxp3WT/Cre heterozygous female mice are unable to rescue the aberrant properties of Tet2/3fl/flFoxp3Cre Treg cells. Treg cells from Tet2/3fl/flFoxp3Cre mice tend to lose Foxp3 expression, and transfer of total CD4+ T cells isolated from Tet2/3fl/flFoxp3Cre mice could elicit inflammatory disease in fully immunocompetent mice. Together, these data indicate that Tet2 and Tet3 are guardians of Treg cell stability and immune homeostasis.

| S-EPMC6494907 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data