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GSE19429
Homo sapiens
200 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathway. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or 7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with 7/del(7q) by pathways involved in cell survival, whilst patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder thereby providing new targets for therapeutic intervention.
Publication Title
Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to gain insight into the poorly understood pathophysiology of the myelodysplastic syndromes (MDS), we have determined the gene expression profiles of the CD34+ cells of 55 MDS patients using the Affymetrix GeneChip U133 Plus2.0 platform
Publication Title
Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype.
Sample Metadata Fields
No sample metadata fields
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- Homo sapiens
- 5 Downloadable Samples
Illumina HiSeq 4000
Description
Here we are using RNA-Seq to study the effect of PRR14L knockdown on transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage. Overall design: RNAseq was performed on individual CFU-GM with shRNA-mediated PRR14L knockdown and scramble control to study the effects of PRR14L knockdown on the transcriptome of hematopoietic cells differentiated towards the granulomonocytic lineage.
Publication Title
PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.
Sample Metadata Fields
Specimen part, Subject
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- Homo sapiens
- 17 Downloadable Samples
- IlluminaHiSeq2000
Description
The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34+ cells from MDS patients with SF3B1 mutations using RNA-sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared to wildtype cases include genes involved in MDS pathogenesis (ASXL1, CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7, SLC25A37) and RNA splicing/processing (PRPF8, HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. Our data indicate that SF3B1 plays a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link. Overall design: RNA-Seq was performed to compare the transcriptome of bone marrow CD34+ cells from eight MDS patients with SF3B1 mutation, four MDS patients with no known splicing mutation and five healthy controls.
Publication Title
Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Gene 1.0 ST Array (chigene10st)
Description
Integrins have long been known to have a role in adhesion of neural stem cells within the neuroepithelium, but little is known about their role in regulating stem cell behaviour through signalling. We aimed to investigate the effect of integrin-beta 1 signalling (itgb1) on these cells by transfection of a constitutively active itgb1. This creates a heterogenous pattern of expression allowing the study of cell-autonomous and non-cell autonomous effects.
Publication Title
Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We applied a novel approach of parallel transcriptional analysis of multiple, highly fractionated stem and progenitor populations in a genetically defined subset of AML (AML with monosomy 7). We isolated phenotypic long-term HSC (LT-HSC), short-term HSC (ST-HSC), and committed granulocyte-monocyte progenitors (GMP) from individual patients with AML, and measured gene expression profiles of each population, and in comparison to their phenotypic counterparts from age-matched healthy controls.
Publication Title
Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We applied a novel approach of parallel transcriptional analysis of multiple, highly fractionated stem and progenitor populations from patients with acute myeloid leukemia (AML) and a normal karyotype. We isolated phenotypic long-term HSC (LT-HSC), short-term HSC (ST-HSC), and committed granulocyte-monocyte progenitors (GMP) from individual patients, and measured gene expression profiles of each population, and in comparison to their phenotypic counterparts from age-matched healthy controls.
Publication Title
Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression analysis on purified human long-term hematopoietic stem cells (LT-HSC; CD34+CD38-CD90+) and short-term HSC (ST-HSC; CD34+CD38-CD90-) derived from healthy control patients and patients with myelodysplastic syndrome (MDS)
Publication Title
Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples