Nitric oxide regulates plant development and responses to stress. However, the mechanisms underlying its regulatory role are still poorly known, and the impact of endogenous NO on the genome-wide transcriptome of plants has not been studied. For that purpose, we compared the transcriptomes of NO-deficient nia1nia2, noa1-2 and nia1nia2noa1-2 mutant versus wild type Arabidopsis thaliana plants. A core comprising 66 NO-responsive genes with similar expression in all NO-deficient genotypes was identified. Among them, 46 were down- and 20 up-regulated in NO-deficient plants, and thus positively and negatively regulated by endogenous NO, respectively. Accordingly with changes in its transcriptome, the NO-deficient nia1nia2noa1-2 mutant accumulated anthocyanins and indolic glucosinolates, displayed abnormal iron homeostasis in shoots and roots, and also showed altered root sensitivity to hormones such as ABA, ET, CYK and IAA. Together the presented data suggest NO functions essentially as a modulator of hormone action.
Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors.
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 used microarrays to investigate gene expression changes in tumor-bearing Pax5+/- mice
Infection Exposure is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of Pax5-Inherited Susceptibility.
Specimen part
View SamplesUnderstanding the underlying mechanisms of the well-established platelet hyporeactivity in neonates, would be of great relevance for both improving the clinical management of neonates, a population with a higher bleeding risk than adults (especially among sick and preterm infants), and getting new insights onto the regulatory mechanisms of platelet biology. Transcriptome analysis is a useful tool to identify mRNA signature affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never been reported. Here, we used, for the first time, mRNA expression array to compare the platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories.
Comprehensive comparison of neonate and adult human platelet transcriptomes.
Specimen part
View SamplesSoil salinity increasingly causes crop losses worldwide. Although roots are the primary targets of salt stress, the signaling networks that facilitate metabolic reprogramming to induce stress tolerance are less understood than those in leaves. Here, a combination of transcriptomic and metabolic approaches was performed in salt-treated Arabidopsis thaliana roots, which revealed that the group S1 basic leucine zipper transcription factors bZIP1 and bZIP53 reprogram primary C- and N-metabolism. In particular, gluconeogenesis and amino acid catabolism are affected by these transcription factors. Importantly, bZIP1 expression reflects cellular stress and energy status in roots. In addition to the well-described abiotic stress response pathway initiated by the hormone abscisic acid (ABA) and executed by SnRK2 (Snf1-RELATED-PROTEIN-KINASE2) and AREB-like bZIP factors, we identify a structurally related ABA-independent signaling module consisting of SnRK1s and S1 bZIPs. Crosstalk between these signaling pathways recruits particular bZIP factor combinations to establish at least four distinct gene expression patterns. Understanding this signaling network provides a framework for securing future crop productivity.
Crosstalk between Two bZIP Signaling Pathways Orchestrates Salt-Induced Metabolic Reprogramming in Arabidopsis Roots.
Specimen part
View SamplesMutations in the gene encoding the transcription factor AutoImmune REgulator (AIRE) are responsible for the Autoimmune PolyEndocrinopathy Candidiasis Ecodermal Dystrophy syndrome. AIRE directs expression of tissue restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE-deficiency leads to impaired deletion of autospecific T cell precursors. However, a potential role for AIRE in the function of regulatory T cell populations, which are known to play a central role in prevention of immunopathology, has remained elusive. Regulatory T cells of CD8+CD28low phenotype efficiently control immune responses in experimental autoimmune and colitis models in mice. We here show that CD8+CD28low Treg from AIRE-deficient mice are transcriptionally and phenotypically normal, exert efficient suppression of in vitro immune responses, but completely fail to prevent experimental colitis in vivo. Our data therefore demonstrate that AIRE plays an important role in the in vivo function of a naturally occurring regulatory T cell population.
Autoimmune regulator (AIRE)-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis.
Treatment
View SamplesThe iron chelator deferasirox is widely used in patients with iron overload. Patients with low-grade myelodysplastic syndromes (MDS) get transfusion dependency and need to be treated with deferasirox to avoid iron overload. Moreover, in some patients an increase in both erythroid and platelets have been observed after deferasirox therapy. However, the mechanisms involved in these clinical findings are poorly understood. The aim of this work was to analyze, in patients treated with deferasirox, the changes in the gene expression profile after receiving the treatment. A total of fifteen patients with the diagnosis of low-grade MDS were studied. Microarrays were carried out in RNA from peripheral blood before and after 14 weeks of deferasirox therapy. Changes in 1,457 genes and 54 miRNAs were observed: deferasirox induced the downregulation of genes related to the Nf kB pathway leading of an overall inactivation of this pathway. In addition, the iron chelator also downregulated gamma interferon. Altogether these changes could be related to the improvement of erythroid response observed in these patients after therapy. Moreover, the inhibition of NFE2L2/ NRF2, which was predicted in silico, could be playing a critical role in the reduction of reactive oxygen species (ROS). Of note, miR-125b, overexpressed after deferasirox treatment, could be involved in the reduced inflammation and increased hematopoiesis observed in the patients after treatment. In summary this study shows, for the first time, the mechanisms that could be governing deferasirox impact in vivo.
Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients.
Specimen part, Disease, Treatment, Subject
View Samples