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GSE17316
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcription factor induced reprogramming of one specialized cell type into another is a promising approach for regenerative medicine. However, the process still remains poorly understood, in large part because of the lack of adequate experimental models. Here we describe a robust cell reprogramming system consisting of a B cell line with an inducible form of C/EBPa that can be converted into macrophages with essentially 100% efficiency in only 2 to 3 days. The conversion involves reciprocal changes in cell surface antigen expression, increase in cell granularity and size, alterations in cellular structures, formation of membrane extensions, acquisition of phagocytic capacity and an increased inflammatory responsiveness as well as migratory activity. Analysis of the transcriptome shows complex reciprocal regulation of B cell and macrophage genes, including transcription factors required for the formation of the two lineages. The fact that the cells become irreversibly committed to a macrophage fate within 1 to 2 days after activation of C/EBPa show that they are truly reprogrammed. The system should be useful to study epigenetic and cell biological mechanisms of transcription factor induced cell reprogramming.
Publication Title
A robust and highly efficient immune cell reprogramming system.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify genes involved in survival to prolonged hypoxia we exposed HCT116 to hypoxia for 3 days. Control cells were exposed to normoxic conditions.
Publication Title
Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells.
Sample Metadata Fields
Disease, Disease stage, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In this study, we use pre-malignant cells from different Cebpa mutant acute myeloid leukemia (AML) models. We have used conditional KO models (CreLoxP) and isolated hematopoietic cells shortly after induction of recombination, in order to look at pre-leukemic cells, which have acquired the first hit, but not yet undergone full malignant transformation.
Publication Title
Lack of the p42 form of C/EBPα leads to spontaneous immortalization and lineage infidelity of committed myeloid progenitors.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 21 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Modulation of several waves of gene expression during FGF-1 induced Epithelial-mesenchymal transition of carcinoma cells . In vitro FGF-1 induced EMT study using NBTII rat bladder carcinoma cells
Publication Title
Modulation of several waves of gene expression during FGF-1 induced epithelial-mesenchymal transition of carcinoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Translocations involving the MLL genes are frequently found in Acute Myeloid Leukemia (AML) and are associated with poor prognosis. The MLL fusion proteins act as aberrant transcription factor activating a transcriptional program that transforms the cells, potentially through collaboration with other transcription factors. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBP to be up-regulated in the AML samples, suggesting that C/EBP might collaborate with MLL fusion proteins in the initial transformation process. We could show that transformation by MLL fusion proteins is dependent on C/EBP activity both in early progenitors as well as in GMPs. In contrast, C/EBP was found to be indispensable in an already established leukemia. These results suggest that C/EBP play an important role in the early transforming event of leukemogenesis.
Publication Title
Initiation of MLL-rearranged AML is dependent on C/EBPα.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in Acute Myeloid Leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that “non-mutated” splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This led to the identification of the splicing regulator RBM25 as a novel tumor suppressor, and down-regulation of RBM25 increased proliferation and decreased apoptosis in human leukemic cell lines. Mechanistically, we could show that RBM25 controlled the splicing of key genes, including those encoding the apoptotic regulator BCL-x and the MYC inhibitor BIN1. Specifically, we demonstrated that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels. This mechanism also appears to be operative in human AML patients where RBM25 levels correlative inversely with MYC activity and clinical outcome. Overall design: Examined transcriptome from U937 cells in biological triplicates.
Publication Title
The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The aim of the study was to investigate the role of TGIF1 in MLL-AF9 transformed cells
Publication Title
TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version)
Description
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. Using this model, we show that the primary effect of Tet2 loss in pre-leukemic hematopoietic cells is progressive and widespread DNA hypermethylation affecting up to 25% of active enhancer elements. In contrast, CpG island and promoter methylation does not change in a Tet2-dependent manner, but increase relative to population doublings. We confirm this specific enhancer hypermethylation phenotype in human AML patients with TET2 mutations. Analysis of immediate gene expression changes reveals rapid deregulation of a large number of genes implicated in tumorigenesis, including many downregulated tumor suppressor genes. Hence, we propose that TET2 prevents leukemic transformation by protecting enhancers from aberrant DNA methylation, and that it is the combined silencing of several tumor suppressor genes in TET2-mutated hematopoietic cells that contribute to increased stem cell proliferation and leukemogenesis.
Publication Title
Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We isolated hematopoietic stem and progenitor cells from AML patients by FACS.
Publication Title
Cellular origin of prognostic chromosomal aberrations in AML patients.
Sample Metadata Fields
Specimen part
View Samples