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GSE51402
Homo sapiens
16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Aberrant activation of -catenin is a common event in Acute Myeloid Leukemia (AML), and is recognized as an independent predictor of poor prognosis. Although increased -catenin signaling in AML has been associated with AML1-ETO and PML-RAR translocation products, and activating mutations in the FLT3 receptor, it remains unclear which mechanisms activate -catenin in AML more broadly. Here, we describe a novel link between interleukin-3 (IL-3) signaling and the regulation of -catenin in myeloid transformation and AML. Using a murine model of HoxB8 and IL-3 cooperation we show that IL-3 modulates -catenin protein levels, and Cre-induced deletion of -catenin abolishes IL-3 dependent growth and colony formation. In the erythroleukemic cell line TF-1.8, we observed increased -catenin protein levels and nuclear localization in response to IL-3, which correlated with transcriptional induction of -catenin target genes. Furthermore, IL-3 promoted -catenin accumulation in a subset of AML patient samples, and microarray gene expression analysis of these cells revealed induction of WNT/-catenin and TCF4 transcriptional gene signatures in an IL-3 dependent manner. This study is the first to link -catenin activation to IL-3 and suggests that targeting IL-3 signaling may be an effective approach for the inhibition of -catenin activity in some patients with AML.
Publication Title
Interleukin-3-mediated regulation of β-catenin in myeloid transformation and acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Publication Title
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Human Exon 1.0 ST Array (huex10st)
Description
Alternative RNA splicing analysis in Hep3B cell cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen
Publication Title
Hypoxia regulates alternative splicing of HIF and non-HIF target genes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 117 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), characterized by aneuploidy and poor outcome, is unknown. Here, using complementary genome-wide profiling approaches, we show that hypodiploid ALL comprises two major subtypes that differ in the severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24-31 chromosomes frequently harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL cases with 32-39 chromosomes are characterized by TP53 alterations (88%), almost half of which are present in non-tumor cells, and have alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras and PI3K signaling pathways, and are sensitive to PI3K inhibition, indicating that these drugs should be explored as a new therapeutic strategy for this frequently lethal form of leukemia.
Publication Title
The genomic landscape of hypodiploid acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 41 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profiling was performed of Pax5 wild type bone marrow subsets from common lymphoid progenitors through to Hardy stage F cells. These cells were obtained by flow sorting of bone marrow.
Publication Title
The genomic landscape of hypodiploid acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 171 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A new method for amplification and labeling of RNA is assessed that permits gene expression microarray analysis of formalin-fixed paraffin embedded tissue (i.e. FFPET) samples.
Publication Title
A novel method of amplification of FFPET-derived RNA enables accurate disease classification with microarrays.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dicer deficiency reveals microRNAs predicted to control gene expression in the developing adrenal cortex.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MicroRNAs (miRNAs) are small, endogenous, non-protein coding RNAs that are an important means of post-transcriptional gene regulation. Deletion of Dicer, a key miRNA processing enzyme, is embryonic lethal in mice, and tissue-specific Dicer deletion results in developmental defects. Using a conditional knockout model, we generated mice lacking Dicer in the adrenal cortex. These Dicer knockout (KO) mice exhibited perinatal mortality and failure of the adrenal cortex during late gestation between embryonic day 16.5 (E16.5) and E18.5. Further study of Dicer KO adrenals demonstrated a significant loss of Sf1 expressing cortical cells that was histologically evident as early as E16.5 coincident with an increase in p21 and cleaved-caspase 3 staining in the cortex. However, peripheral cortical proliferation persisted in KO adrenals as assessed by anti-PCNA staining. To further characterize the embryonic adrenals from Dicer KO mice, we performed microarray analyses for both gene expression and miRNA on purified RNA isolated from control and KO adrenals of E15.5 and E16.5 embryos. Consistent with the absence of Dicer and the associated loss of miRNA-mediated mRNA degradation, we observed an up-regulation of a small subset of adrenal transcripts in Dicer KO mice, most notably the transcripts coded by the genes Nr6a1 and Acvr1c. Indeed, several miRNAs, including let-7, miR-34c, and miR-21 that are predicted to target these genes for degradation, were also markedly down-regulated in Dicer KO adrenals. Together these data suggest a role for miRNA mediated regulation of a subset of genes that are essential for normal adrenal growth and homeostasis.
Publication Title
Dicer deficiency reveals microRNAs predicted to control gene expression in the developing adrenal cortex.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P.
Publication Title
Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation, and pluripotency in human embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Glycine max
- 26 Downloadable Samples
Illumina HiSeq 2000
Description
Soybean (Glycine max) seeds are an important source of seed storage compounds, including protein, oil, and sugar used for food, feed, chemical, and biofuel production. We assessed detailed temporal transcriptional and metabolic changes in developing soybean embryos to gain a systems biology view of developmental and metabolic changes and to identify potential targets for metabolic engineering. Two major developmental and metabolic transitions were captured enabling identification of potential metabolic engineering targets specific to seed filling and to desiccation. The first transition involved a switch between different types of metabolism in dividing and elongating cells. The second transition involved the onset of maturation and desiccation tolerance during seed filling and a switch from photoheterotrophic to heterotrophic metabolism. Clustering analyses of metabolite and transcript data revealed clusters of functionally related metabolites and transcripts active in these different developmental and metabolic programs. The gene clusters provide a resource to generate predictions about the associations and interactions of unknown regulators with their targets based on guilt-by-association relationships. The inferred regulators also represent potential targets for future metabolic engineering of relevant pathways and steps in central carbon and nitrogen metabolism in soybean embryos and drought and desiccation tolerance in plants. Overall design: Total mRNA profiles of 10 time course samples of Soybean developing embryos with three replicates per sample were generated by deep sequencing, using Illumina HiSeq 2000
Publication Title
Transcriptome-wide functional characterization reveals novel relationships among differentially expressed transcripts in developing soybean embryos.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples