This experiment was carried out in the context of a pharmacogenetic study of long-term (4-year follow-up) response to Interferon-beta treatment in two cohorts of Italian Multiple Sclerosis patients, to identify genetic variants (SNPs) that may influence response to IFN-beta. We integrated results from meta-analysis of the two cohorts with gene expression profiling of IFN stimulated PBMCs from 20 healthy controls and eQTL analyses, to look at possible enrichment of IFN-beta induced genes with genes mapped by top-ranking meta-analyzed SNPs.
Pharmacogenetic study of long-term response to interferon-β treatment in multiple sclerosis.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesWe report the global gene expression of mouse pancreatic cells in a pancreas-specific conditional knock-out mouse for Gata6, as compared with age-matched controls. Total RNA was extracted from the pancreas of 6-8 -week old mice of the two genotypes and analyzed. at this age, Gata6P-/- pancreata are histologically normal, but the acinar differentiation programme is already altered. we observe that loss of Gata6 causes the de-repression of ectopic non-pancreatic genes, as well as some genes involved in the mesenchymal programme. Overall design: mRNA extracted from the pancreas of 4 controls and 4 Gata6P-/- mice was sequenced.
The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice.
Specimen part, Cell line, Subject
View SamplesWe 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.
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.
No sample metadata fields
View SamplesAmong B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.
Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.
No sample metadata fields
View SamplesTo identify genes associated with citrus peel development and manifestation of peel disorders, we analyzed flavedo, albedo and juice sac tissues from five types of citrus fruit including, mandarin orange, navel orange, valencia orange, grapefruit and lemon.
Transcriptome and metabolome analysis of citrus fruit to elucidate puffing disorder.
Specimen part
View SamplesRNA-sequencing performed on petals and inflorescence of Arabidopsis plants. The study provides insight into the role of the TCP5 transcription factor and its molecular mechanism underlying petal growth, using knock-out, overexpression and induction lines on which RNA-sequencing was performed. Overall design: Analysis of differential gene expression using petals from TCP5 overexpression and knockout lines, as well as inflorescences of an inducible TCP5 mutant.
Novel functions of the Arabidopsis transcription factor TCP5 in petal development and ethylene biosynthesis.
Specimen part, Subject
View SamplesTo identify genes associated with citrus peel development and manifestation of peel disorders, we analyzed flavedo, albedo and juice sac tissues from navel orange displaying, and not displaying, the puff disorder.
Transcriptome and metabolome analysis of citrus fruit to elucidate puffing disorder.
Specimen part
View SamplesRNA-binding proteins participate in a complex array of post-transcriptional controls essential to cell-type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts on mammalian embryonic development remains incompletely defined and the level of functional redundancy among subsets of these proteins remains open to question. The poly-(C) binding proteins, Pcbp's (aCPs, hnRNPEs), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos survive until mid-gestation at which time they undergo a loss in viability associated with cardiovascular and hematopoietic abnormalities. Adult mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and non-disruptive growth defect. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and post-natal growth, reveal a non-redundant in vivo role for Pcpb2 in hematopoiesis, and provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved essential function(s) in the mammalian genome. Overall design: mRNA-seq on fetal liver tissue from 12.5 days post coitum. 4 replicates of WT and 3 replicates of PCBP2 Knockout
Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript.
Age, Subject
View SamplesTranscriptome analysis of two Ph+ acute lymphoblastic leukemia cell lines after doxycycline induced silencing of MYB.
Targeting CDK6 and BCL2 Exploits the "MYB Addiction" of Ph<sup>+</sup> Acute Lymphoblastic Leukemia.
Cell line
View SamplesHere we used microarray expression profiling to characterise global changes in gene expression during stages of proliferation and differentiation of human neural stem cells
Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval.
Specimen part, Cell line
View Samples