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GSE6184
Homo sapiens
32 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Anaplastic Large Cell Lymphomas (ALCL) represent a subset of lymphomas in which the Anaplastic Lymphoma Kinase (ALK) gene is frequently fused to the NPM gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo, and that ALK activity is strictly required for the survival of ALK positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK positive ALCL cell lines abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell permeable ALK inhibitors. Transcripts derived from the gene expression profiling (GEP) analysis uncovered a reproducible signature, which included a novel group of ALK-regulated genes. Functional RNAi screening on a set of these ALK transcriptional targets revealed that the transcription factor C/EBPb and the anti-apoptotic protein BCL2A1 are absolutely necessary to induce cell transformation and/or to sustain the growth and survival of ALK positive ALCL cells. Thus, we proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions.
Publication Title
Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
eIF4E, the major cap-binding protein, has long been considered limiting for translating the mammalian genome. However, the requirement for eIF4E dose at an organismal level remains unexplored. By generating an Eif4e haploinsufficient mouse, we surprisingly found that 50% reduction in eIF4E, while compatible with normal development and global protein synthesis, significantly impeded cellular transformation and tumorigenesis. Genome-wide translational profiling uncovered a translational program induced by oncogenic transformation and revealed a critical role for eIF4E dose specifically in translating a network of mRNAs enriched for a unique 5UTR signature. In particular, we demonstrate that eIF4E dose is essential for translating mRNAs regulating reactive oxygen species (ROS) that fuel transformation and cancer cell survival in vivo. Therefore, mammalian cells have evolved surplus eIF4E levels that cancer cells hijack to drive a translational program supporting tumorigenesis
Publication Title
Differential Requirements for eIF4E Dose in Normal Development and Cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
MIST1 is a bHLH transcription factor that is necessary for the maturation of gastric zymogenic cells as they differentiate from their precursor mucous neck cells. In this experiment, mucous neck cells and zymogenic cells of normal, adult C57BL/6 and MIST1 knockout mice were laser-capture microdissected in order to determine MIST1-dependent, zymogenic cell specific gene expression.
Publication Title
The ubiquitin ligase Mindbomb 1 coordinates gastrointestinal secretory cell maturation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We have undertaken a screen of mouse limb tendon cells in order to identify molecular pathways involved in tendon development. Mouse limb tendon cells were isolated based on Scleraxis (Scx) expression at different stages of development: E11.5, E12.5 and E14.5
Publication Title
Transcriptomic analysis of mouse limb tendon cells during development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Here we used microarray expression profiling to characterise global changes in gene expression during stages of proliferation and differentiation of human neural stem cells
Publication Title
Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression of Double Positive, and Single Positive CD4+ human thymocytes
Publication Title
Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genetic studies have shown that human T-ALLs can be divided into subgroups that are characterized by unique gene expression signatures and relate to stages of T-cell differentiation at which the leukemic cells arrest. Each molecular subgroup has characteristic genetic abnormalities that cause aberrant activation of specific T-ALL transcription factor oncogenes, including LYL1/MEF2C, HOXA, TLX1, TLX3 and TAL1/LMO2. Notably, the recently described Early T-cell Precursor ALL (ETP-ALL) patients have leukemic cells that show an early block in T-cell differentiation and significantly overlap with LYL1-positive T-ALL and MEF2C-dysregulated immature T-ALL. We studied the gene expression profiles of 64 primary T-ALL samples and found a high BCL-2 expression in immature T-ALL patients compared to patients belonging to other subgroups.
Publication Title
ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bivalent histone domains have been proposed to contribute to pluripotency in embryonic stem cells, suggesting an epigenetic mechanism may regulate stem cell behavior in general. Here we compare histone modifications in two other stem cells derived from the blastocyst. We show that extraembryonic stem cells have little repressive lysine 27 trimethylation and few bivalent domains. Thus, bivalent domains are not a common mechanism for maintaining the undifferentiated state in blastocyst-derived stem cells and alternative mechanisms must mediate transcriptional repression in extraembryonic cells. We show that lysine 9 trimethylation, but not DNA methylation, is likely to fulfill this role. Intriguingly, although we do detect bivalent domains in pluripotent cells in the early mouse embryo, the epigenetic status of extraembryonic cells does not entirely reflect their in vitro stem cell counterparts. Therefore, differences in epigenetic regulation between lineage progenitors in vivo and in vitro may arise during selection for self-renewal in vitro.
Publication Title
Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo.
Sample Metadata Fields
Cell line
View Samples- Macaca mulatta
- 13 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 4 mo old rhesus macaques subject to maternal rearing, peer rearing, or surrogate peer rearing. The primary research question is whether gene expression differs as a function of early rearing conditions.
Publication Title
Transcriptional modulation of the developing immune system by early life social adversity.
Sample Metadata Fields
Age
View Samples