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GSE73066
Homo sapiens
35 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pilocytic astrocytoma is the most common type of brain tumor in pediatric population, generally connected with favorable prognosis, although recurrences or dissemination sometimes are also observed. For tumors originating in supra- or infratentorial location different molecular background was suggested but plausible correlations between transcriptional profile and radiological features and/or clinical course are still undefined. The purpose of this study was to identify gene expression profiles related to the most frequent locations of this tumor, subtypes based on various radiological features and clinical pattern of the disease. According to the radiological features presented on MRI, all cases were divided into four subtypes: solid or mainly solid, cystic with an enhancing cyst wall, cystic with a non-enhancing cyst wall and solid with central necrosis. Bioinformatic analyses showed that gene expression profile of pilocytic astrocytoma highly depends on the tumor location. Most prominent differences were noted for IRX2, PAX3, CXCL14, LHX2, SIX6, CNTN1 and SIX1 genes expression which could distinguish pilocytic astrocytomas of different location even within supratentorial region. Analysis of the genes potentially associated between radiological features showed much weaker transcriptome differences. Single genes showed association with the tendency to progression. Here we showed that pilocytic astrocytomas of three different locations could be precisely differentiated on the basis of gene expression level but their transcriptional profiles did not strongly reflect the radiological appearance of the tumor or the course of the disease.
Publication Title
Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Two nuclear 5'-3' exonucleases XRN2/3 in Arabidopsis thaliana are homologs of the yeast and human Rat1/Xrn2, which are involved in degradation and processing of several classes of nuclear RNAs and in transcription termination of RNA polymerase II. Here we show that knockdown of XRN3 leads to altered expression of several hundred of the Arabidopsis genes and accumulation of new non-coding RNAs. Using strand-specific short read sequencing we reveal a widespread accumulation of intergenic transcripts in xrn3 mutants. These non-coding XAT (xrn3-associated transcripts) RNAs are generated by Pol II read-through transcription and are usually polyadenylated and lack the 5' cap structure. We show that XRN3-mediated changes in expression of a subset of genes are related to XAT transcription and may be enhanced by XAT-mRNA chimeras produced in xrn3 plants while antisense XATs may trigger siRNA production. Our results highlight the important role of the Rat1/Xrn2 5'-3' exoribonucleases in the torpedo mechanism of Pol II transcription termination and show that a global disturbance in this process significantly impacts both gene expression and transcriptome integrity.
Publication Title
Defective XRN3-mediated transcription termination in Arabidopsis affects the expression of protein-coding genes.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Danio rerio
- 26 Downloadable Samples
IlluminaHiSeq2000
Description
We used different zebrafish transgenic lines to sort macrophages, neutrophils and immature lymphoid cells from 5-6 day old zebrafish larvae and analyzed their transcriptomes. Comparison between the different transcriptomes and gene ontology analysis revealed specificities for each cell population. Comparison with previously published data showed that zebrafish larval macrophages expressed several known human M1 and M2 macrophages. Transcriptome analysis of uninfected and infected macrophages from embryos infected by of Mycobacterium marinum revealed infection induced transcriptional changes and a shift towards M1 transcriptomic signature. Overall design: Embryos were grown into egg water refresh every day and incubated for 5 or 6 days at 28°C. 0.003% 1-phenyl-2-thiourea (Sigma-Aldrich) was added after 1 day to prevent melanisation. After the incubation period, embryos were dissociated into single cell suspension by Trypsin treatment and fluorescent cells were sorted by FACS. RNA extraction and library preparation were performed as previously described. (Rougeot et al., 2014, Methods Mol Biol 1197:41-66). For infection experiments, zebrafish embryos were manually dechorionated at 24 hours post fertilization (hpf) and were infected by injection in the caudal vein of 125 colony forming unit of Mycobacterium marinum M strain expressing GFP. Infected larvae were collected for FACS sorting 5 day post infection.
Publication Title
Corrigendum: RNAseq Profiling of Leukocyte Populations in Zebrafish Larvae Reveals a <i>cxcl11</i> Chemokine Gene as a Marker of Macrophage Polarization During Mycobacterial Infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of genes that differentially expressed in CSLC cells compared with non-CSLC cells, which are derived from the same parental MDA-MB453 cell line.
Publication Title
Molecular characteristics of cancer stem-like cells derived from human breast cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Ubiquitylation of histones provides an important mechanism regulating chromatin remodeling and gene expression. Recent studies have revealed ubiquitin ligases involved in histone ubiquitylation, yet the responsible enzymes and the function of histone ubiquitination in spermatogenesis remain unclear. Here we show that the ubiquitin ligase UBR2, one of the recognition E3 components of the N-end rule proteolytic pathway, localizes to meiotic chromatin regions, including unsynapsed axial elements linked to chromatin inactivation, and mediates, in combination with the ubiquitin-conjugating enzyme HR6B, the ubiquitination of histone H2A. UBR2 interacts with HR6B and H2A and promotes the HR6B-H2A interaction and the HR6B-to-H2A transfer of ubiquitin. UBR2 and ubiquitinated H2A (uH2A) spatiotemporally mark meiotic chromatin regions subject to transcriptional silencing, and UBR2-deficient spermatocytes fail to induce the ubiquitination of H2A during meiosis. UBR2-deficient spermatocytes are profoundly impaired in transcriptional silencing of genes linked to unsynapsed axes of the X and Y chromosomes. We propose a model, in which UBR2 on axial elements of the X-Y pair enables HR6B on the linked chromatin domain to repeat histone ubiquitination cycles while scanning a string of nucleosomes. Our results suggest that histone ubiquitination in germ cells may be mediated by E3-E2 pairs distinct from those in somatic cells, providing a new insight into chromatin remodeling and gene expression regulation.
Publication Title
UBR2 mediates transcriptional silencing during spermatogenesis via histone ubiquitination.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Whole exome sequencing identified frequent driver mutations in a series of paediatric glioblastomas
Publication Title
Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins.
Publication Title
Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
In this work we have analyzed the transcriptomic profiles of E9 mouse embryos. We show that Hoxd1 and Haglr transcripts are absent after targeted deletion of the CpG: 114 island. Overall design: RNA-seq analysis of trunk from the anterior limit of the forelimb bud to the tailbud, aiming to exclude all extra-embryonic, head, cervical and heart tissues. Individuals 443 (wt) and 445 (Del(CpG114) homozygous), were siblings from the same dam, while biological replicates 456 (wt) and 455 (Del(CpG114) homozygous) were siblings from another dam.
Publication Title
Control of growth and gut maturation by <i>HoxD</i> genes and the associated lncRNA <i>Haglr</i>.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of NOD, NOD.Rag1-/-, and B6.g7 mice at three weeks of age. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II both at the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced a rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them. In NOD mice, the autoimmune process imparted an increased inflammatory signature, including elevated expression of chemokines, chemokine receptors, and an oxidative response. The elevated inflammatory signature indicates that the autoimmune program was active at the time of weaning. Thus, the macrophages of the islets of Langerhans are poised to mount an immune response even at steady state, while the presence of the adaptive immune system elevates their activation state. Overall design: We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of NOD, NOD.Rag1-/-, and B6.g7 mice at three weeks of age. Lung macrophages and pancreatic LN dendritic cells of NOD mice were also examined.
Publication Title
The islet-resident macrophage is in an inflammatory state and senses microbial products in blood.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Abnormal NF-kB2 activation has been reported in several types of human leukemia and lymphomas although the exact mechanisms and affected pathways are not clear. We have investigated these questions through the use of a unique transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma associated NF-kB2 mutant. Microarray analysis, verified at the RNA and protein level identified new downstream targets and confirmed established regulatory networks. 201 genes were significantly changed, with 126 being upregulated and 75 downregulated. Pathway analysis uncovered both known and unknown interactions between factors important in the development of human B cell lymphomas and multiple myeloma, including cyclins D1 and D2, TRAF1, CD27, BIRC5/survivin, IL-15 and IL-10. Critical roles for STAT3 and TNF receptors are highlighted. Six target genes of STAT3 were identified: cyclins D1and D2, IL-10, survivin, IL-21 and Blimp1. Interfering with STAT3 signaling induced apoptosis in multiple myeloma cell lines. Novel pathways for NF-kB2 are proposed that involve IL-10 and other genes in the differentiation of plasma cells, evasion of apoptosis and proliferation. These pathways were verified with publically available human microarrays. Several treatment strategies based on these findings are discussed.
Publication Title
NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors.
Sample Metadata Fields
Specimen part
View Samples