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GSE73474
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dectin1 controls the recruitment of TLR9 to -1,3 glucan beads containing phagosomes. We sought to determine whether Dectin-1 also plays a role in controlling TLR9 dependent gene expression.
Publication Title
Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing β-1,3 Glucan.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to assess the physiological role of Cop1 in vivo we generated mice that do no longer express the protein. Cop1KO mice die at around E10.5 of embryonic development. In order to gain insights into the molecular mechanisms that cause the embryonic death we compared the genome-wide gene expression profile of E9.5 wild-tytpe and Cop1-null embryos. The data do not support a role for Cop1 in the regulation of the p53 pathway in vivo and highlight a role for Cop1 in cardiovascular development and/or angiogenesis. The abstract of the associated publication is as follows:Biochemical data have suggested conflicting roles for the E3 ubiquitin ligase Cop1 in tumourigenesis. Here we present the first in vivo investigation of the role of Cop1 in cancer aetiology. We used an innovative genetic approach to generate an allelic series of Cop1 and show that Cop1 hypomorphic mice spontaneously develop malignancy at a high frequency in their first year of life and are highly susceptible to radiation-induced lymphomagenesis. Biochemically, we show that Cop1 regulates c-Jun oncoprotein stability and modulates c-Jun/AP1 transcriptional activity in vivo. Cop1-deficiency stimulates cell proliferation in a c-Jun-dependent manner. We conclude that Cop1 is a tumour suppressor that antagonizes c-Jun oncogenic activity in vivo.
Publication Title
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 168 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We aimed to determine the impact of the common mutations on the transcriptome in myelodysplastic syndromes (MDS). We linked genomic data with gene expression microarray data and we deconvoluted the expression of genes into contributions stemming from each genetic and cytogenetic alteration, providing insights into how driver mutations interfere with the transcriptomic state. We modelled the influence of mutations and expression changes on diagnostic clinical variables as well as survival.
Publication Title
Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes.
Sample Metadata Fields
Specimen part, Disease
View Samples- Danio rerio
- 8 Downloadable Samples
IlluminaHiSeq2500
Description
We report the gene expression comparison of zebrafish melanocytes and melanomas. These comparisons were used for integrative genomic studies that identified the BMP factor GDF6 as a new oncogene that is specifically expressed in melanomas. Overall design: Examination of gene expression in two different cell types
Publication Title
Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 80 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.
Publication Title
Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
FLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors
Publication Title
FLT3-ITDs instruct a myeloid differentiation and transformation bias in lymphomyeloid multipotent progenitors.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Mutations of the splicing factor U2AF1 are frequent in the myeloid malignancy myelodysplastic syndromes (MDS) and in other cancers. Patients with MDS suffer from peripheral blood cytopenias, including anemia, and increasing bone marrow blasts. We investigated the impact of the common U2AF1 S34F mutation on cellular function and mRNA splicing in the main cell lineages affected in MDS. We demonstrated that U2AF1 S34F expression in human hematopoietic progenitors impairs erythroid differentiation, and skews granulomonocytic differentiation towards granulocytes. RNA-sequencing of erythroid and granulomonocytic colonies revealed that U2AF1 S34F induced a higher number of cassette exon splicing events in granulomonocytic than erythroid cells, and altered mRNA splicing of many transcripts (expressed in both cell types) in a lineage-specific manner. The introduction of isoform changes identified in the target genes H2AFY and STRAP into hematopoietic progenitors recapitulated phenotypes associated with U2AF1 S34F expression in erythroid and/or granulomonocytic cells, suggesting a causal link. Importantly, we provided evidence showing that isoform modulation of the U2AF1 S34F target genes H2AFY and STRAP rescues the erythroid differentiation defect in U2AF1 S34F MDS cells, raising the possibility of using splicing modulators therapeutically. These data have critical implications for understanding MDS phenotypic heterogeneity, and for the development of new targeted therapies. Overall design: RNA sequencing was performed to identify the aberrant splicing events associated with U2AF1 S34F mutation (n=3) compared to U2AF1 wild-type (n=3) and empty vector control (n=3) in BFU-E and CFU-G/M colonies respectively.
Publication Title
The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 42 Downloadable Samples
- Illumina HiSeq 2500
Description
Using integrated genomics we identify a role for CLEC12A in antibacterial autophagy. Clec12a-/- mice are more susceptible to bacterial infection and CLEC12A deficient cells exhibit impaired antibacterial autophagy. We used transcriptional profilinf to understand the role of CLEC12A in the response to Salmonella and Listeria. Overall design: Bone marrow-derived macrophages from WT or Clec12a-/- mice were infected with Salmonella enterica serovar Typhimurium or Listeria monocytogenes. Cells were harvested at 0,3,6, and 24hours post-infection for RNA analysis. Please note that single-end sequencing was performed but two files: R1 files that contained the sample barcodes (19 or 17bp reads) and R2 files that contained the single-end-sequenced 46bp cDNA reads were generated. Since the barcode info is mostly redundant, only R2 reads were submitted (described in ''raw_file_readme.txt'').
Publication Title
Integrated Genomics of Crohn's Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
CD34 positive cells of bone marrow samples from normal and MDS samples were cultured ex vivo into erythroid conditions.
Publication Title
Defective nuclear localization of Hsp70 is associated with dyserythropoiesis and GATA-1 cleavage in myelodysplastic syndromes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 765 Downloadable Samples
- Illumina HiSeq 4000
Description
SF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in MDS. We have performed a comprehensive analysis to determine the impact of these commonly mutated splicing factors on pre-mRNA splicing in the stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in bone marrow CD34+ cells of a large group of 82 MDS patients. Splicing factor mutations in MDS result in different mechanistic alterations in splicing and largely affect different genes, but these converged in common dysregulated pathways and cellular processes, including RNA splicing, translation and mitochondrial dysfunction, indicating that these mutations operate through common mechanisms in MDS. Many of these dysregulated pathways and cellular processes can be linked to the known disease pathophysiology and to the phenotypes associated with splicing factor mutations in MDS, whilst several others have not been previously associated with MDS, such as sirtuin signalling. Overall design: RNA-sequencing was performed on bone marrow CD34+ hematopoeitic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls to identify differential splicing between samples with mutations in the splicing factor SF3B1, SRSF2 or U2AF1 comparative to samples from myelodysplactic syndrome patients without mutations in these splicing factors and healthy controls. Processed data for the CD34+ hematopoeitic stem and progenitor cells are available in the files: CPM_table.txt.gz, Count_table.txt.gz and TPM_table.txt.gz. RNA-sequencing was also performed on monocytic, granulocytic and erythroid precursors from the bone marrow of patients with myelodysplastic syndrome and healthy controls to identify aberrant splicing in samples with mutations in splicing factors SF3B1 and SRSF2 comparative from healthy controls. Processed data for the monocytic, granulocytic and erythroid precursors are available in the files: CPM_table_fractions.txt, Count_table_fractions.txt and TPM_table_fractions.txt.
Publication Title
Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples