Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Acute loss of TET function results in aggressive myeloid cancer in mice [RNA-Seq]

ABSTRACT: TET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumor suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. We show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukemia in mice, pointing to a causative role for TET-loss-of-function in this myeloid malignancy. Phenotypic and transcriptional profiling showed aberrant differentiation of hematopoietic stem/ progenitor cells, impaired erythroid and lymphoid differentiation and strong skewing to the myeloid lineage, with only a mild relation to changes in DNA modification. We also observed progressive accumulation of DNA damage and strong impairment of DNA break repair, suggesting a key role for TET proteins in maintaining genomic integrity.

ORGANISM(S): Mus musculus

PROVIDER: GSE72628 | GEO | 2015/11/26

SECONDARY ACCESSION(S): PRJNA294517

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch [WGBS]

Project description:The three mammalian TET dioxygenases oxidize the methyl group of 5-methylcytosine (5mC) in DNA, and the oxidised methylcytosines are essential intermediates in all known pathways of DNA demethylation. To define the in vivo consequences of complete TET deficiency, we inducibly deleted all three Tet genes in the mouse genome. Tet1/2/3 inducible TKO (iTKO) mice succumbed to acute myeloid leukaemia by 4-5 weeks. Single-cell RNA sequencing of Tet iTKO bone marrow cells revealed the appearance of new myeloid cell populations characterised by a striking increase in expression of all members of the stefin/cystatin gene cluster on mouse chromosome 16. In patients with acute myeloid leukaemia, high stefin/cystatin gene expression correlates with poor clinical outcomes. Increased expression of the clustered stefin/cystatin genes was associated with a heterochromatin-to-euchromatin compartment switch with readthrough transcription downstream of the clustered stefin/cystatin genes as well as other highly expressed genes but only minor changes in DNA methylation. Our data highlight new roles for TET enzymes that are distinct from their established function in DNA demethylation, and instead involve increased transcriptional readthrough and changes in three-dimensional genome organisation.

2023-04-18 | GSE222725 | GEO

Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch [Hi-C]

2023-04-18 | GSE222719 | GEO

Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch [ATAC-seq]

2023-04-18 | GSE222718 | GEO

Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch [scRNA-seq]

2023-04-18 | GSE222722 | GEO

Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch [polyA+ RNA-seq]

2023-04-18 | GSE222720 | GEO

Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch [Ribodepleted RNA-seq]

2023-04-18 | GSE222721 | GEO

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

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 | GSE72116 | GEO

Differential RNA expression profiling in response to TET inhbition

Project description:Ten-to-Eleven Translocation (TET) family of proteins oxidize 5mC in to 5hmC on the genomic DNA and act as interesting class of epigenetic medulators. A novel small molecule inhbitor of TET enzymatic activity, C35 is developed.

2019-12-31 | GSE137282 | 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