This SuperSeries is composed of the SubSeries listed below.
High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.
Specimen part, Disease, Disease stage
View SamplesUsing high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Notably, deletion or uniparental disomy of chromosome 7q were detected in 39% of SMZLs but in only 9 of 170 (5%) mature B-cell lymphomas (p<10-6). The presence of unmutated IgVH genes, genomic complexity, 17p13-P53 deletion and 8q gain including MYC gene, but not 7q deletion, were correlated with shorter overall survival. Extensive mapping analyses narrowed down the commonly deleted region to 2.7 Mb. in 7q32.1-q32.2 from SND1 to COPG2 genes. High-throughput sequencing analysis of the 7q32 deleted segment in SMZL cells did not identify bi-allelic deletions, insertions or clear pathogenic mutations, but detected six single nucleotide changes in IRF5 (n=2), TMEM209 (n=2), CALU (n=1) and ZC3HC1 (n=1). Comparative expression analysis found that IRF5, TMEM209 and CALU genes had down-regulated expression in lymphomas with 7q32 deletion vs. non-deleted tumors. Ectopic expression of IRF5 in marginal-zone lymphoma cells decreased cell proliferation and induced apoptosis. These results indicate that small deletions, insertions and/or point mutations inactivating genes within 7q32 are not common events in SMZL. Further studies are required to evaluate the putative role of IRF5 in SMZL pathogenesis.
High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.
Disease, Disease stage
View SamplesThe alveolar type 1 (AT1) cell covers >95% of the gas exchange surface and is extremely thin to facilitate passive gas diffusion. The development of this highly specialized cell is poorly understood including fundamental questions regarding cell number and morphology. Using new molecular stereology and single cell imaging methods, we show that AT1 cells develop via a non-proliferative two-step process while maintaining proliferative potential. In the flattening step, AT1 cells remodel cell junctions and undergo molecular specification. In the folding step, AT1 cells are sculptured to match secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. AT1 cells grow in size by >10-fold, fueling most of the postnatal lung growth. Strikingly AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results contradict the traditional view of AT1 cells being terminally differentiated and provide insights to alveolar maturation. In this experiment, we conducted next-generation sequencing on flow-sorter AT1 cells isolated from mouse lungs ectopically expressing Sox2 under the control of the AT1-specific promoter Scnn1a versus control AT1 cells. Overall design: Two samples of Sox2-expressing AT1 cells versus two control AT1 samples.
The development and plasticity of alveolar type 1 cells.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles.
Specimen part
View SamplesCyclic regulatory systems are ubiquitous in cells and tissues. In the liver rhythms in mRNA expression are determined by the homeostatic regulation that operates on daily circumstances. In particular the specific response to nutrients, as well as systemic and peripheral circadian oscillators, contribute to the set up of the hepatic homeostasis at different phases of the day. In this series we used microarrays to detail the global program of gene expression in the mouse liver under physiological daily variations, determined by both the feeding and the circadian cycles.
Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease
View SamplesAttempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NF-kappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease
View SamplesComparison of gene expression profiling analysis of bone marrow isolated CD34+ cells from patients with MALT lymphoma vs. healthy individuals revealed a large number of differentially expressed genes that included NF-kB target genes, genes involved in inflamatory signalling and immunoglobulin genes, suggesting an early lymphoid B-cell priming.
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease, Disease stage
View SamplesAttempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NFkappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Specimen part, Disease
View SamplesWe previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53, Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. We have adapted these GEM models to orthotopic allografts that uniformly develop tumors with short latency in immunocompetent recipients and are ideally suited for routine preclinical studies. To monitor passaged tumors at the molecular level, we analyzed transcriptional profiles of a set of primary SEOC and matching derived passaged tumors. We have merged this dataset with previously published ( doi: 10.1158/0008-5472.CAN-11-3834; PMID 22617326) dataset of murine primary ovarian tumors from our GEM models (GSE46169) and merged and compared them to expression profiles of human dataset published previously (doi: 10.1038/nature10166).
Pathway-specific engineered mouse allograft models functionally recapitulate human serous epithelial ovarian cancer.
Specimen part
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