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GSE138236
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Glioblastomas (GBM) are brain tumors which display a bad prognosis despite conventional treatment associating surgical resection and subsequent radio-chemotherapy. These tumors are defined by an abundant and abnormal vascularization as well as by an important cellular heterogeneity. GBM notably contain a subpopulation of GBM stem-like cells (GSC) which contribute to tumor aggressiveness, resistance, and recurrence. Moreover, GSC directly take part in the formation of new vessels via their transdifferentiation into tumor derived endothelial cells (TDEC). Considering the importance of the vascularization in the GBM, we postulate that radiation could enhance the transdifferentiation of GSC into TDEC. Here, we show that ionizing radiation potentiates endothelial features of TDEC obtained from 3 patient-derived primocultures of GSC. Indeed, TDEC obtained from irradiated GSC (TDEC IR+) migrate more towards VEGF, form more pseudotubes in Matrigel in vitro and develop more functional blood vessel in Matrigel plugs implanted in Nude mice than TDEC obtained from non-irradiated GSC. Transcriptomic analysis allows us to highlight an overexpression of Tie2 in TDEC IR+ which is associated with the activation of AKT signaling pathway. All radiation-induced effects on TDEC IR+ were abolished by using a Tie2 kinase inhibitor, confirming the role of Tie2 signaling pathway in this process. Finally, the number of Tie2+ vessels is increased in recurrent GBM compared with matched untreated tumors. In conclusion, we show that irradiation potentiates proangiogenic features of TDEC throught Tie2/AKT signaling pathway. New therapeutic stategies associating standard teatment and an inhibitor of Tie2 signaling pathway should be considered for forthcoming trials.
Publication Title
Ionizing radiation induces endothelial transdifferentiation of glioblastoma stem-like cells through the Tie2 signaling pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Alternative mRNA splicing is a major mechanism for gene regulation and transcriptome diversity. Despite the extent of the phenomenon, the regulation and specificity of the splicing machinery are only partially understood. Adenosine-to-inosine (A-to-I) RNA editing of pre-mRNA by ADAR enzymes has been linked to splicing regulation in several cases. Here we used bioinformatics approaches, RNA-seq and exon-specific microarray of ADAR knockdown cells to globally examine how ADAR and its A-to-I RNA editing activity influence alternative mRNA splicing. Although A-to-I RNA editing only rarely targets canonical splicing acceptor, donor, and branch sites, it was found to affect splicing regulatory elements (SREs) within exons. Cassette exons were found to be significantly enriched with A-to-I RNA editing sites compared with constitutive exons. RNA-seq and exon-specific microarray revealed that ADAR knockdown in hepatocarcinoma and myelogenous leukemia cell lines leads to global changes in gene expression, with hundreds of genes changing their splicing patterns in both cell lines. This global change in splicing pattern cannot be explained by putative editing sites alone. Genes showing significant changes in their splicing pattern are frequently involved in RNA processing and splicing activity. Analysis of recently published RNA-seq data from glioblastoma cell lines showed similar results. Our global analysis reveals that ADAR plays a major role in splicing regulation. Although direct editing of the splicing motifs does occur, we suggest it is not likely to be the primary mechanism for ADAR-mediated regulation of alternative splicing. Rather, this regulation is achieved by modulating trans-acting factors involved in the splicing machinery. Overall design: HepG2 and K562 cell lines were stably transfected with plasmids containing siRNA designed to specifically knock down ADAR expression (ADAR KD). This in order to examine how ADAR affects alternative splicing globally.
Publication Title
Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR).
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR).
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alternative mRNA splicing is a major mechanism for gene regulation and transcriptome diversity. Despite the extent of the phenomenon, the regulation and specificity of the splicing machinery are only partially understood. Adenosine-to-inosine (A-to-I) RNA editing of pre-mRNA by ADAR enzymes has been linked to splicing regulation in several cases. Here we used bioinformatics approaches, RNA-seq and exon-specific microarray of ADAR knockdown cells to globally examine how ADAR and its A-to-I RNA editing activity influence alternative mRNA splicing. Although A-to-I RNA editing only rarely targets canonical splicing acceptor, donor, and branch sites, it was found to affect splicing regulatory elements (SREs) within exons. Cassette exons were found to be significantly enriched with A-to-I RNA editing sites compared with constitutive exons. RNA-seq and exon-specific microarray revealed that ADAR knockdown in hepatocarcinoma and myelogenous leukemia cell lines leads to global changes in gene expression, with hundreds of genes changing their splicing patterns in both cell lines. This global change in splicing pattern cannot be explained by putative editing sites alone. Genes showing significant changes in their splicing pattern are frequently involved in RNA processing and splicing activity. Analysis of recently published RNA-seq data from glioblastoma cell lines showed similar results. Our global analysis reveals that ADAR plays a major role in splicing regulation. Although direct editing of the splicing motifs does occur, we suggest it is not likely to be the primary mechanism for ADAR-mediated regulation of alternative splicing. Rather, this regulation is achieved by modulating trans-acting factors involved in the splicing machinery.
Publication Title
Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR).
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of major groups of AML fusion oncogenes on primary human CD34+ cells.
Publication Title
In vitro transformation of primary human CD34+ cells by AML fusion oncogenes: early gene expression profiling reveals possible drug target in AML.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Glucocorticoids (GCs) and protein kinase A (PKA)-activating agents (beta-adrenergic receptor agonists) are mainstream asthma therapies based on their ability to prevent or reverse excessive airway smooth muscle (ASM) constriction. Their abilities to regulate another important feature of asthma - excessive ASM growth are poorly understood. Recent studies have suggested that GCs render agents of inflammation such as interleukin 1beta and tumor necrosis factor alpha mitogenic to ASM, via suppression of (antimitogenic) induced cyclooxygenase-2-dependent PKA activity. To further explore the mechanistic basis of these observations, we assessed the effects of epidermal growth factor and interleukin 1beta stimulation, and the modulatory effects of GC treatment and PKA inhibition, on the ASM transcriptome by microarray analysis.
Publication Title
Glucocorticoid- and protein kinase A-dependent transcriptome regulation in airway smooth muscle.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Ion Torrent S5
Description
We investigated whether in vitro expansion of human alveolar epithelial type II cells is possible. We found that human endogenous human alveolar epithelial type II cells can be cultured and passaged. The culture system enabled retroviral gene transduction into human alveolar epithelial type II cells. We performed RNA sequencing of human alveolar epithelial type II cells transduced with mutant surfactant protein C or control vector. Overall design: Cultured human alveolar epithelial type II cells were transfected with retroviral vector containing mutant surfactant protein C or control retroviral vector. The retroviral vector contained LNGFR as a marker. After gene transduction, transduced cells were purified by magnetic-activated cell sorting. The transcriptome of the cells was generated by 5'Tag-seq using Ion Genestudio S5 Sequencer.
Publication Title
In vitro expansion of endogenous human alveolar epithelial type II cells in fibroblast-free spheroid culture.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
It has been shown that inbred strains of mice exhibit variable susceptibility to S. aureus infection, but the specific genes responsible for this differential phenotype are unknown. Using ISHM to identify genomic regions associated with the phenotypes, we considered genes within those interval to be candidate genes and used the gene expression patterns of the genes contained in the region to determine whether the genes are differentially expressed between the 2 phenotypically different groups of mice.
Publication Title
Haplotype Association Mapping Identifies a Candidate Gene Region in Mice Infected With Staphylococcus aureus.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina HiSeq 4000
Description
Single-cell analysis of KPC pancreatic tumor cells Overall design: Evaluate the single-cell transcriptomic landscape in 3 KPf/fC tumors
Publication Title
A Multiscale Map of the Stem Cell State in Pancreatic Adenocarcinoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples