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SRP114773
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 4000
Description
Human T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization. Overall design: mRNA profiles of T-cells obtained from hu-Mice infected with wild-type or Tax-PBM HTLV-1 were generated by deep-sequencing in triplicates using Illumina's Hiseq3000 platform.
Publication Title
PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Burkitt lymphoma is the commonest cancer in children in Africa. We compared the gene expression profiles of African Burkitt lymphoma patients with those of cases presented in Western countries in both immunocompetent (sporadic Burkitt lymphoma) and HIV-infected patients (immunodeficiency associated Burkitt lymphoma).
Publication Title
Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of the determinants of PDGFRA activity in PTCL/NOS (Peripheral T-cell lymphoma/not otherwise specified) and to elucidate the biological consequences of its activation.
Publication Title
Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
During malaria infection is observed a robust immune response culminating on release of inflammatory mediators. This exacerbated immune response is involved in malaria symptoms and mortality. There are evidences that this response is mediated by innate immunity where pattern recognition receptors have a key role. We used microarrays to elucidate some pro-inflammatory genes that are differential expressed during P. chabaudi infection, a malarial murine model
Publication Title
Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-binding proteins participate in a complex array of post-transcriptional controls essential to cell-type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts on mammalian embryonic development remains incompletely defined and the level of functional redundancy among subsets of these proteins remains open to question. The poly-(C) binding proteins, Pcbp's (aCPs, hnRNPEs), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos survive until mid-gestation at which time they undergo a loss in viability associated with cardiovascular and hematopoietic abnormalities. Adult mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and non-disruptive growth defect. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and post-natal growth, reveal a non-redundant in vivo role for Pcpb2 in hematopoiesis, and provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved essential function(s) in the mammalian genome. Overall design: mRNA-seq on fetal liver tissue from 12.5 days post coitum. 4 replicates of WT and 3 replicates of PCBP2 Knockout
Publication Title
Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript.
Sample Metadata Fields
Age, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
An efficient innate immune recognition of the intracellular parasite T. cruzi is crucial for host protection against development of Chagas disease, which often leads to multiple organ damage, particularly the heart leading to cardiomyopathy. Mechanisms modulated by MyD88 have been shown to be necessary for resistance against T, cruzi infection. Recently, Nod-like receptors have been shown to play an important role as innate immune sensors, particularly as they relate to inflammasome function, caspase activation, and inflammatory cytokine production. In this study, we aimed to investigate the participation of innate immune responses in general, and inflammasomes in particular, in heart inflammation and cardiac damage upon infection with the T. cruzi parasite.
Publication Title
Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β response and host resistance to Trypanosoma cruzi infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Patients with febrile malaria were recruited in order to determine Peripheral Blood Mononuclear Cell (PBMC) gene expression during malaria. Blood was harvested from patients during the acute phase of the illness, and then patients were given a curative regimen of antimalarials. Three to four weeks after treatment, patients returned to the malaria clinic and blood was collected again, in order that each patient could serve as his or her own control. PBMC were isolated at the time of blood collection and forzen in RNA extraction buffer. At the end of the study, each patient was arrayed for ~47,000 transcripts, comparing gene expression at the end of therapy to that at the beginning. The goal was to determine which genes were altered as a result of disease at least 2 fold in a statistically significant manner and to assess if the genes involved could be related to Toll-like receptor signaling pathways. Approximately 60 genes involved in inflammation were confirmed by qPCR.
Publication Title
Malaria primes the innate immune response due to interferon-gamma induced enhancement of toll-like receptor expression and function.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
Human male infertility has long been associated with genetic defects that affect nuclear RNA binding proteins, yet what RNA targets these proteins control or why their absence causes infertility remain poorly defined. Here we find that genetic knockout of the mouse nuclear RNA binding protein gene Hnrnpgt causes azoospermia. Knockout male germ cells arrest during the highly transcriptionally active stage of meiotic prophase with altered meiotic nuclear RNA processing patterns. Hnrnpgt knockout most notably leads to the inclusion of previously unidentified cryptic exons that could otherwise disable gene function and poison the meiotic transcriptome. Hnrnpgt target genes include Esco1 and Kdm4d, which encode proteins that are important for chromosome function, and Hnrnpgt null germ cells have altered centromere clustering and H3K9me3 distribution patterns. Our data reveal a nuclear RNA processing programme that is critical for meiotic metaphase entry. Overall design: Gene expression profiling by RNA-Seq of mouse testes 18 days post-partum. Samples from C57BL/6 background, either wild type (n=3) or HnRNPGT Cre-Lox knockout (n=3).
Publication Title
An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing them to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present in every comparison. These genes were enriched in RNA processing pathways and encoded ~100 SFs, e.g. hnRNPA1. hnRNPA1 3'UTR was most pervasively misspliced, yielding the transcript subject to nonsense-mediated decay. Thus, we knocked it down in B-lymphoblastoid cells, identified 213 hnRNPA1-dependent splicing events, and defined the hnRNPA1 splicing signature in pediatric leukemias. One of its elements was DICER1, a known tumor suppressor gene; its LSVs involved the 5' UTR, suggestive of splicing as a mechanism of translational deregulation. Additionally, we searched for LSVs in other leukemia and lymphoma drivers and discovered 81 LSVs in 41 genes. 77 LSVs were confirmed using two large independent B-ALL RNA-seq datasets. In fact, the twenty most common B-ALL drivers showed higher prevalence of aberrant splicing than of somatic mutations. Thus, post-transcriptional deregulation of SF can drive widespread changes in B-ALL splicing and likely contribute to disease pathogenesis. Overall design: We profiled hnRNPA1 Ctrl and hnRNPA1 knockdown with 2 replicates each.
Publication Title
Aberrant splicing in B-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Some 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.
Publication Title
CD1d-restricted peripheral T cell lymphoma in mice and humans.
Sample Metadata Fields
Age, Specimen part
View Samples