Mice with a congenital Snord116 deletion model aspects of the Prader-Willi Syndrome. In this study, we examine the gene expression changes in four hypothalamic nuclei across 24-hour food deprived versus ad libitum fed mice. Overall design: Using mice with paternal deletion of the Snord116 cluster, we laser-captured microdissected four hypothalamic nuclei for RNA sequencing: the ventromedial hypothalamus (VMH), arcuate nucleus (ARC), dorsomedial hypothalamus (DMH) and paraventricular nucleus (PVN). Samples were taken from male mice in either the fed or 24-hour fasted state.
Hypothalamic loss of Snord116 recapitulates the hyperphagia of Prader-Willi syndrome.
Cell line, Subject
View SamplesHIV+ Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4+ T cells with resistance specific to R5-tropic HIV, reversed after introduction of CCR5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4+ T cells of these EC/VCs had lower CCR2 and CCR5 mRNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of CCR2 and CCR5, despite having more accessible chromatin by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq). Other nearby genes were also down-regulated, over a region of ~500kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with CCR2/CCR5 down-regulation, suggesting that the phenotype is heritable. Overall design: RNA-seq was performed to identify up- or down-regulated genes associated with in vitro resistance to R5-tropic viruses in activated CD4+ T cells from HIV+ Elite Controllers and family members
Transcriptional down-regulation of <i>ccr5</i> in a subset of HIV+ controllers and their family members.
Specimen part, Subject
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesThe genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that likely account for the varying survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator (GEDI) algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity (CNN-LOH) is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes such as CUL4A, ING1 and MCPH1 may affect the two crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL, since decreased expression of its members MOBKL2A, MOBKL2B and LATS2 was associated with inferior outcome also in an independent validation series of 32 MCL.
Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling.
Disease, Disease stage, Subject
View SamplesFollicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.
Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.
Specimen part, Disease, Disease stage, Subject
View SamplesGene expression data for shRNA PTPN1 knockdown vs. Non-silencing in the classical Hodgkin lymphoma-derived cell line KM-H2
Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma.
Specimen part, Cell line
View SamplesThe assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B-cell-like (GCB) or activated B-cell-like (ABC) groups. The LLMPP's Lymph2Cx assay is a parsimonious digital gene-expression (NanoString) based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) routinely produced in standard diagnostic processes. The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort the assay was accurate, with only one case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turn-around-time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management.
Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesMonocytes are key players in inflammatory processes which are triggered by lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria. The present study in human monocytic THP-1 cells was designed in order to identify LPS-inducible genes which are down-regulated by the reduced form of CoQ10 (ubiquinol, Q10H2). For this purpose, THP-1 cells were incubated with 10 M Q10H2 for 24 h. Subsequently, cells were stimulated for 4 h with 1g/ml LPS and the resulting gene expression levels were determined using microarrays. 14 LPS-inducible genes were identified to be significantly (p < 0.05) down-regulated by Q10H2 pre-treatment between a factor of 1.32 and 1.65. The strongest effect of Q10H2 incubation was found for the nuclear receptor coactivator 2 gene (NCOA2). Gene Ontology (GO) terms revealed for the Q10H2-sensitive genes an involvement in e.g. signal transduction processes (CENTD1, NCOA2, PSD3, PPP2R5C), transcriptional regulation (NCOA2, POU2F1, ETV3) and cell proliferation pathways (CCDC100, EPS15). In conclusion, we provide evidence in THP-1 cells that the reduced form of CoQ10 (Q10H2) modulates LPS-induced gene expression.
The reduced form of coenzyme Q10 decreases the expression of lipopolysaccharide-sensitive genes in human THP-1 cells.
Specimen part
View Samples