Microglia depletion significantly lowered spine density in young (developing) but not mature adult-born-granule-cells (abGCs) in the olfactory bulb. PLX5622 significantly reduces microglia related gene transcripts. Overall design: We tested mouse olfactory bulb transcription in WT mice versus mice treated with a PLX5622 diet (inducing a near-complete microglia depletion).
The role of microglia and their CX3CR1 signaling in adult neurogenesis in the olfactory bulb.
Specimen part, Cell line, Subject
View SamplesMice 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 SamplesSepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality.
Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation.
Sex, Age, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Targeting androgen receptor in estrogen receptor-negative breast cancer.
Disease, Disease stage, Cell line, Time
View SamplesAnalysis of MDA-MB-453 breast cancer cells treated with the androgen 5a-dihydrotestosterone (DHT) for 6h, 16h and 48h to define the genes that are differentially regulated in response to DHT.
Targeting androgen receptor in estrogen receptor-negative breast cancer.
Disease, Disease stage, Cell line, Time
View SamplesOncogene-induced DNA methylation-mediated transcriptional silencing of tumor suppressors frequently occurs in cancer, but the mechanism and functional role of this silencing in oncogenesis is not fully understood. Here, we show that oncogenic epidermal growth factor receptor (EGFR) induces silencing of multiple unrelated tumor suppressors in lung adenocarcinomas and glioblastomas by inhibiting DNA demethylase TET oncogene family member 1 (TET1) via the C/EBP transcription factor. After oncogenic EGFR inhibition, TET1 binds to tumor suppressor promoters and induces their re-expression via active DNA demethylation. Ectopic expression of TET1 potently inhibits lung and glioblastoma tumor growth, and TET1 knockdown confers resistance to EGFR inhibitors in lung cancer cells. Lung cancer samples exhibited reduced TET1 expression or TET1 cytoplasmic localization in a majority of cases. Collectively, these results identify a conserved pathway of oncogenic EGFR-induced DNA methylation-mediated transcriptional silencing of tumor suppressors, which may have therapeutic benefit for oncogenic EGFR-mediated lung cancers and glioblastomas.
Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells.
Cell line
View SamplesStat5a and Stat5b proteins are highly homologous with greater than 90% amino acid identity and share binding to the palindromic Stat5 consensus sequence, TTCNNNGAA, but individual roles of each transcription factor in breast cancer have not been thoroughly evaluated. To determine the degree of similarity between transcripts modulated by Stat5a and Stat5b proteins in human breast cancer, we utilized genome-wide transcript profiling to identify genes regulated specifically by Stat5a or Stat5b in response to prolactin.
Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes.
Cell line
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 SamplesTumorigenic breast cancer cells characterized by high CD44 and low or undetectable CD24 levels (CD44+/CD24-/low) may be resistant to conventional therapies and responsible for cancer relapse. We defined a signature expression pattern of hundreds of genes associated with CD44+/CD24-/low, mammosphere-forming cells. In a panel of patient breast tumors, this tumorigenic gene signature was found exclusively manifested in tumors of the recently identified claudin-low molecular profile subtype characterized by overexpression of many mesenchymal-associated genes, suggesting that these tumors have pre-existing higher levels of tumorigenic cells. Furthermore, when comparing the expression profiles of paired breast cancer core biopsies before versus after hormone therapy or chemotherapy, both the tumorigenic and claudin-low signatures were more active in about half of tumors after treatment, indicative of a greater enrichment of tumorigenic cells as a result of treatments targeting the bulk tumor cells.
Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features.
Sex, Specimen part, Treatment
View Samples