We investigated the biological features of FL and their relationship to patients outcome. Gene expression analysis was carried out on diagnosis biopsies from 148 follicular lymphoma patients enrolled in the PRIMA clinical trial. We developed a gene expression-based predictor of progression-free survival (PFS) in high-tumour burden FL patients and we analysed gene-expression signatures reflecting different aspects of tumour biology for their association with outcome. proposition SH: We investigated the biological features of FL and their relationship to patients outcome. Gene expression analysis was carried out on diagnosis biopsies from 148 follicular lymphoma patients enrolled in the PRIMA clinical trial. We developed a gene expression-based predictor of progression-free survival (PFS) in high-tumour burden FL patients and we analysed gene-expression signatures reflecting different aspects of tumour biology for their association with outcome.
A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts.
Sex, Specimen part
View SamplesSome infectious agents are associated with non-Hodgkin lymphoma development. Here we have used p53-deficient mice chronically injected with Streptococcus pneumoniae (Spn) with the aim to develop an animal model of infection-associated lymphomagenesis. We show that repeated stimulations with heat-killed Spn significantly enhanced the incidence of peripheral T-cell lymphoma (PTCL) in these mice. Phenotypic studies and gene expression profile analyses indicate that these PTCL arose from chronically stimulated natural killer T (NKT) cells, a T cell lineage that exhibits unique properties. Furthermore, lymphoma development was blocked when these PTCL were transferred to recipients lacking CD1d expression or treated with blocking CD1d mAbs, thus demonstrating that in vivo TCR/CD1d interactions are required for these PTCL survival. In conclusion, we have identified a new entity of peripheral T-cell lymphoma that originates from CD1d-restricted natural killer T (NKT) cells. Our results could refine the classification of PTCL and pave the way for the development of new immunotherapeutic approaches.
CD1d-restricted peripheral T cell lymphoma in mice and humans.
Age, Specimen part
View SamplesHeterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Overall design: Single cell RNAseq of cells isolated from their in vivo niche in the subventricular zone, Striatum and Cortex during homeostasis as well as following ischemic injury. In total 272 single cells. (<WT>: homeostasis samples; <Ischemic_injured> and <Ischemic_injured_and_Interferon_gamma_knockout>: samples following ischemic injuried).
Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.
No sample metadata fields
View SamplesPatients with metastatic colorectal cancer were enrolled for treatment with cetuximab monotherapy. Transcriptional profiling was conducted on RNA from pre-treatment metastatic site biopsies to identify genes whose expression correlates with best clinical responses.
Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.
Specimen part
View SamplesSox2 is required to maintain osteosarcoma cell tumor initiation.Knockdown of Sox2 leads tpo loss of tumorigenic properties. To examine gene expression changes upon Sox2 knockdown, we performed microarray analysis on mouse osteosarcoma cells expressing scrambled or Sox2shRNA. We found that genes upregulated upon Sox2 knockdown included osteoblast diffrentiation genes and genes down regulated included cell cycle and RNA processing genes as well as YAP-TEAD target genes.
Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells.
Specimen part, Cell line
View SamplesThe Mediator complex regulates gene transcription by linking basal transcriptional machinery with DNA-bound transcription factors. The activity of the Mediator complex is mainly controlled by a kinase submodule that is comprised of four proteins, including MED12. Although ubiquitously expressed, Mediator subunits can differentially regulate gene expression in a tissue-specific manner. Here, we report that MED12 is required for normal cardiac function such that mice with conditional cardiac-specific deletion of MED12 display progressive dilated cardiomyopathy. Loss of MED12 perturbs expression of calcium handling genes in the heart, consequently altering calcium cycling in cardiomyocytes and disrupting cardiac electrical activity. We identified transcription factors that regulate expression of calcium-handling genes that are downregulated in the heart in the absence of MED12, and found that MED12 localizes to transcription factor consensus sequences within calcium handling genes. We showed that MED12 interacts with one such transcription factor, MEF2, in cardiomyocytes, and that MED12 and MEF2 co-occupy promoters of calcium handling genes. Furthermore, we demonstrated that MED12 enhances MEF2 transcriptional activity and overexpression of both increases expression of calcium handling genes in cardiomyocytes. Our data support a role for MED12 as a coordinator of transcription through MEF2 and other transcription factors. We conclude that MED12 is a regulator of a network of calcium handling genes, consequently “mediating” contractility in the mammalian heart. Overall design: Ventricle mRNA profiles of 1-day old control (CTL, CreNEG) and cardiac-specific Med12 knockout mice (Med12cKO, CrePOS) were generated by deep sequencing, in triplicate, using Illumina.
MED12 regulates a transcriptional network of calcium-handling genes in the heart.
No sample metadata fields
View SamplesAnaplastic large-cell lymphoma (ALCL) makes up approximately 15% of paediatric non-Hodgkin's lymphomas of childhood. The vast majority of them is associated with the t(2;5)(p23;q35) translocation that results in the expression of a hybrid oncogenic tyrosine kinase, NPM-ALK. In order to investigate ALCL biological characteristics we used transcriptional profiling approach. Genome-wide gene expression profiling, performed on 23 paediatric ALCL and 12 reactive lymph nodes specimens, showed two novel ALCL subgroups based on their NPM-ALK expression levels (named (ALK low and ALK high). Gene set enrichment analysis revealed, in ALK low samples, a positive enrichment of genes involved in the Interleukin signaling pathway, whereas we found increased expression of genes related to cell cycle progression and division in ALK high tumour samples, such as Aurora Kinase A (AURKA) and B (AURKB). Growth inhibition was observed upon administration of AURKA and AURKB inhibitors Alisertib and Barasertib and it was associated with perturbation of the cell cycle and induction of apoptosis. In conclusion we identified two novel ALCL subgroups, which display unique biological characteristics suggesting sensitivity to distinct targeted therapies.
NPM-ALK expression levels identify two distinct subtypes of paediatric anaplastic large cell lymphoma.
No sample metadata fields
View SamplesAcute lymphoblastic pediatric leukemia specimens without known genetic hallmarks are examined for hidden genomic aberrancies and related gene expression profiles
Integration of genomic and gene expression data of childhood ALL without known aberrations identifies subgroups with specific genetic hallmarks.
No sample metadata fields
View SamplesThe heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously showed that cardiac MED13 modulates systemic energy homeostasis in mice. Here we sought to define the extra-cardiac tissue(s) that respond to cardiac MED13 signaling. We show that cardiac over-expression of MED13 in transgenic (MED13cTg) mice confers a lean phenotype that is associated with increased lipid uptake, beta-oxidation and mitochondrial content in white adipose tissue (WAT) and liver. Cardiac expression of MED13 decreases metabolic gene expression and metabolite levels in heart and liver but enhances them in WAT. Although exhibiting increased energy expenditure in the fed state, MED13cTg mice metabolically adapt to fasting. Furthermore, MED13cTg hearts oxidize fuel that is readily available, rendering them more efficient in the fed state. Parabiosis experiments in which circulations of wild-type and MED13cTg mice are joined, reveal that circulating factor(s) in MED13cTg mice promote enhanced metabolism and leanness. These findings demonstrate that MED13 acts within the heart to promote systemic energy expenditure in extra-cardiac energy depots and point to an unexplored metabolic communication system between the heart and other tissues. Overall design: n=3 for each genotype and organ
MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties.
Specimen part, Treatment, Subject
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