GEO DataSets

Analysis of sorted bone marrow progenitor populations (LSK, CMP, GMP) deficient in ten-eleven translocation 2 (TET2). Tet2 loss causes increased hematopoietic stem cell self-renewal and myeloid transformation. Results provide insight into the molecular mechanisms underlying myeloid malignancies.

Organism:

Mus musculus

Type:

Expression profiling by array, count, 4 cell type, 2 genotype/variation sets

Platform:

GPL1261

Series:

GSE27816

14 Samples

Download data: CEL

(Submitter supplied) Recurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid malignancies and in other cancers. However, the in vivo effects of Tet2 loss have not been delineated. We report here that Tet2 loss leads to increased stem-cell self-renewal and to progressive stem cell expansion. Consistent with human mutational data, Tet2 loss leads to myeloproliferation in vivo, notable for splenomegaly and monocytic proliferation. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS4287

Platform:

GPL1261

14 Samples

Download data: CEL

(Submitter supplied) By using a genetically accurate mouse model, we demonstrate that endogenous expression of oncogenic N-RasG12D and Tet2 haploinsufficiency collaborate to accelerate CMML development in mice. Gene expression was compared across all genotypes (WT, Tet2+/-, NrasG12D/+ and double mutants) in bone marrow-derived hematopoietic stem cells (CD150+CD48-Lin-Sca1+cKit+) using RNA-seq. N-RasG12D and Tet2 haploinsufficiency cooperate to induce both unique and overlapping effects on HSC gene expression programs.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

12 Samples

Download data: TXT

(Submitter supplied) TET2 plays an important role in regulating the behavior of bone marrow derived MSCs in addition to its intrinsic role in HSPCs to participate in aberrant hematopoiesis. Moreover, MSCs are the most important niche cell components in Tet2-/- mice that contribute to the progression of Tet2 deletion-driven myeloid malignancies. This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platform:

GPL17021

8 Samples

Download data: BW

(Submitter supplied) Identification the genome-wide distribution of 5-hmC in WT-MSCs and Tet2-/--MSCs by Genome-wide 5hmc Profiling.

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL17021

4 Samples

Download data: BW

(Submitter supplied) Bone marrow–derived mesenchymal stem/progenitor cell mRNA profiles of WT and Tet2−/− mice were generated by deep sequencing.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

4 Samples

Download data: XLS

(Submitter supplied) To investigate the signaling pathway required for the Tet2 mutant associated clonal hematopoiesis, we identified the activated signaling pathway in Tet2-deficient hematopoietic stem/progenitor cells compared to WT cells and using transgentic mouse model to validate our findings. In short, the cGAS-STING pathway is activated in Tet2-deficient HSPCs and promotes the development of CH associated with Tet2 deficiency.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

55 Samples

Download data: CSV, TXT

(Submitter supplied) To identify genes that are influenced by the catalytic and non-catalytic functions of Tet2 in hematopoietic stem and progenitor cells (HSPCs), we analyzed the gene expression profiles of Tet2 catalytic mutant (Tet2 Mut), Tet2 knockout (Tet2 KO) and wild-type HSPCs (or LSK, Lin–Sca-1+c-Kit+) and multi-potent progenitor (or MPP, Lin–) cells by RNA-seq.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

12 Samples

Download data: TXT

(Submitter supplied) Epigenetic modifying enzymes DNMT3A and TET2 are recurrently mutated in hematological disorders despite possessing opposing biochemical functions in the DNA methylation processes. Using conditional ablation, we show these contrasting genotypes result in different functional effects in hematopoietic stem cells (HSCs). Loss of Dnmt3a bestows enhanced self-renewal on HSCs in serial, competitive repopulation assays while Tet2 loss functionally depletes HSCs after a tertiary transplant despite an initial competitive advantage. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL19057 GPL24247

36 Samples

Download data: BW, TSV

(Submitter supplied) Mutations in the epigenetic modifiers DNMT3A and TET2 non-randomly co-occur in lymphoma and leukemia despite their epistasis in the methylation-hydroxymethylation pathway. Using double knock-out (DKO) mice in which malignancy development is accelerated, we show that the DKO methylome reflects regions of independent, competitive and cooperative activity. Expression of lineage-specific transcription factors, including the erythroid regulator Klf1 is upregulated in DKO HSCs. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Methylation profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

12 Samples

Download data: BED, BW, TXT

(Submitter supplied) DNA methylation is tightly regulated throughout mammalian development and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO induced AML. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL10787

9 Samples

Download data: TXT

(Submitter supplied) DNA methylation is tightly regulated throughout mammalian development and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO induced AML. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

16 Samples

Download data: BED, BIGWIG

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Methylation profiling by high throughput sequencing; Expression profiling by array

Platforms:

GPL16570 GPL13112 GPL10787

53 Samples

Download data: BED, BIGWIG, CEL, TXT

(Submitter supplied) DNA methylation is tightly regulated throughout mammalian development and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO induced AML. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL16570

12 Samples

Download data: CEL

(Submitter supplied) DNA methylation is tightly regulated throughout mammalian development and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO induced AML. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL13112

10 Samples

Download data: TXT

(Submitter supplied) DNA methylation is tightly regulated throughout mammalian development and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO induced AML. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: BED, BIGWIG

(Submitter supplied) Hematopoietic stem cells sustain life-long blood production. While they are the known cellular origin of aging-associated myeloid malignancies, such as acute myeloid leukemia (AML), mechanisms driving their malignant transformation have remained elusive. Epigenetic dysregulation following acquired loss-of-function mutations of DNA methyl-cytosine dioxygenase Ten-Eleven Translocation-2 (TET2) occurs frequently in the elderly leading to cytosine hypermethylation in and around DNA binding sites of master transcription factors, including PU.1. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL21103

16 Samples

Download data: BEDGRAPH

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL21103 GPL17021

41 Samples

Download data: BEDGRAPH

(Submitter supplied) Hematopoietic stem cells sustain life-long blood production. While they are the known cellular origin of aging-associated myeloid malignancies, such as acute myeloid leukemia (AML), mechanisms driving their malignant transformation have remained elusive. Epigenetic dysregulation following acquired loss-of-function mutations of DNA methyl-cytosine dioxygenase Ten-Eleven Translocation-2 (TET2) occurs frequently in the elderly leading to cytosine hypermethylation in and around DNA binding sites of master transcription factors, including PU.1. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21103

8 Samples

Download data: NARROWPEAK

(Submitter supplied) Hematopoietic stem cells sustain life-long blood production. While they are the known cellular origin of aging-associated myeloid malignancies, such as acute myeloid leukemia (AML), mechanisms driving their malignant transformation have remained elusive. Epigenetic dysregulation following acquired loss-of-function mutations of DNA methyl-cytosine dioxygenase Ten-Eleven Translocation-2 (TET2) occurs frequently in the elderly leading to cytosine hypermethylation in and around DNA binding sites of master transcription factors, including PU.1. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

17 Samples

Download data: TXT