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GSE30903
Homo sapiens
22 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study, we investigated whether, and to what extent, P2Rs and their ligands are involved in the regulation of AML cells. Our findings show that AML blasts express several receptors belonging to the P2X and P2Y family. Although different samples respond differently to ATP and UTP stimulation (reflecting the variability intrinsic to the group of acute myeloid leukemias), all the tested samples appear to be responsive to purinergic signalling, as demonstrated by intracellular calcium mobilization.
Publication Title
Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
We show the molecular and functional characterization of a novel population of lineage-negative CD34-negative (Lin- CD34-) hematopoietic stem cells (HSCs) from chronic myelogenous leukemia (CML) patients at diagnosis. Molecular caryotyping and quantitative analysis of BCR/ABL transcript demonstrated that about one third of CD34- was leukemic. CML CD34- cells showed kinetic quiescence and limited clonogenic capacity. However, stroma-dependent cultures and cytokines induced CD34 expression on some HSCs, cell cycling, acquisition of clonogenic activity and increased expression of BCR/ABL transcript. CML CD34- cells showed an engraftment rate in immunodeficient mice similar to that of CD34+ cells. Gene expression profiling revealed the down-regulation of cell cycle arrest genes together with genes involved in antigen presentation and processing, while the expression of angiogenic factors was strongly up-regulated when compared to normal counterparts. Flow cytometry analysis confirmed the significant down-regulation of HLA class I and II molecules in CML CD34-cells. Increasing doses of imatinib mesilate (IM) did not affect fusion transcript levels, BCR-ABL kinase activity and the clonogenic efficiency of CML CD34- cells as compared to leukemic CD34+cells.
Publication Title
Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
NextSeq 500
Description
Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/b-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development. Overall design: RNA-sequencing of peripheral blooof 10 LM patients and 9 control subjects
Publication Title
Alterations of the MEK/ERK, BMP, and Wnt/β-catenin pathways detected in the blood of individuals with lymphatic malformations.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant methylation has been postulated to play an important role in tumorigenesis. We report the use of methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to investigate methylation changes in testicular germ cell tumor (TGCT) cells. Coupled to expression profiling changes, we found that only 22-26% of differentially methylated genes were also expressed differentially. This phenomenon was independent of the presence of CpG islands in the promoter. Differential methylation and expression of some of these genes were confirmed in testicular tumor tissue. A substantial number of differentially methylated regions in the human genome were not linked to annotated gene loci. Subsequent analysis indicated several microRNAs and small nucleolar RNAs were regulated by these differentially methylated regions. Our results demonstrate the power of the combination of MeDIP-chip analysis and expression profiling for discovery in cancer cells of epigenetically regulated genes and non-coding RNAs in cancer cells.
Publication Title
Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Macaca mulatta
- 48 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
The etiology of the central nervous system (CNS) alterations after human immunodeficiency virus (HIV) infection, such as dementia and encephalitis, remains unknown. We have used microarray analysis in a monkey model of neuroAIDS to identify 98 genes, many previously unrecognized in lentiviral CNS pathogenesis, whose expression is significantly up-regulated in the frontal lobe of simian immunodeficiency virus-infected brains. Further, through immunohistochemical illumination, distinct classes of genes were found whose protein products localized to infiltrating macrophages, endothelial cells and resident glia, such as CD163, Glut5, and ISG15. In addition we found proteins induced in cortical neurons (ie, cyclin D3, tissue transglutaminase, 1-antichymotrypsin, and STAT1), which have not previously been described as participating in simian immunodeficiency virus or HIV-related CNS pathology. This molecular phenotyping in the infected brains revealed pathways promoting entry of macrophages into the brain and their subsequent detrimental effects on neurons. These data support the hypothesis that in HIV-induced CNS disease products of activated macrophages and astrocytes lead to CNS dysfunction by directly damaging neurons, as well as by induction of altered gene and protein expression profiles in neurons themselves which are deleterious to their function.
Publication Title
Induction of pathogenic sets of genes in macrophages and neurons in NeuroAIDS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
H3.3 phosphorylation promotes high levels of histone acetylation in mouse embryonic stem cells, which are central to the initiation of new transcription during lineage specification. Overall design: RNA-Seq analysis in mouse embryonic stem cells (Control, H3.3KO, HIRAKO, ATRXKO, DAXXKO) and embryoid bodies at Day 4 of differentiation (Control and H3.3KO).
Publication Title
Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 122 Downloadable Samples
- Illumina HiSeq 4000
Description
Goblet cell metaplasia and mucus hypersecretion are disabling hallmarks of chronic lung diseases for which no curative treatments are available. Therapies targeting specific upstream drivers of asthma have had variable results. We hypothesized that an a priori-knowledge independent approach would point to new therapies for airway goblet cell metaplasia. We analyzed the transcriptome of an organotypic model of human goblet cell metaplasia. We combined our data with previously published datasets from IL13-exposed in vitro and asthmatic in vivo human airway epithelial cells. The drug perturbation-response connectivity approach identified the heat shock protein 90 (HSP90) inhibitor geldanamycin as a candidate for reverting airway goblet cell metaplasia. We found that geldanamycin not only prevented but reverted IL13-induced goblet cell metaplasia. Geldanamycin did not induce goblet cell death, did not solely block mucin synthesis, and did not block IL13 receptor-proximal signaling. Moreover, the transcriptional effects of geldanamycin were absent in unstimulated cells and became evident only after stimulation with IL13. The predicted mechanism of action suggested that geldanamycin should also revert IL17-induced goblet cell metaplasia, a prediction confirmed by our data. Our findings suggest HSP90 activity may be required for persistence of goblet cell metaplasia driven by various mechanisms in chronic lung diseases. Overall design: For both batches, airway epithelia cultures from the lungs of eight different humans were studied, therefore, there are eight biological replicates. Comparisons should be made within batches. In batch 1 (XAM1), epithelia were exposed to vehicle (DMSO 0.5%), geldanamycin 25 uM, or the HDAC6 inhibitor ISOX 10 uM for 48 hours. In batch 2 (XAM3), the epithelia were exposed to vehicle (DMSO 0.5%), IL13 (20 ng/mL) or IL13 plus geldanamycin (10 uM) for 48 hours.
Publication Title
HSP90 inhibitor geldanamycin reverts IL-13- and IL-17-induced airway goblet cell metaplasia.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of nuclear-enriched miRNAs during mouse granulopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Differentiation of hemopoietic stem cells into granulocytes is characterized by distinct changes in the transcriptome.
Publication Title
Identification of nuclear-enriched miRNAs during mouse granulopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/- :Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration. Our finding that the type I hair cells were absent in the mutants cristae was further used here to identify a profile of genes specific to the lacking cell type.
Publication Title
Role of skeletal muscle in ear development.
Sample Metadata Fields
Specimen part
View Samples