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SRP118806
Mus musculus
12 Downloadable Samples
NextSeq 500
Description
The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2 (CerS2) null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of iNKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for iNKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in iNKT cell physiology. Overall design: Liver mRNA profiles of 3-4 month old wild type (WT), WT iNKT cell transfered and CerS2-/-mice, infected or not with LCMV were generated by deep sequencing. Several replicateswere included and pocessed using the MARS-seq protocol (Jaitin et al. 2014 Science.343:776-9) and sequencing in the Illumina NextSeq 500 instrument
Publication Title
Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary effusion lymphoma is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposis sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients yet efforts to develop superior therapeutic approaches have been impeded by lack of animal models that more accurately mimic human disease. To address this issue we developed a direct xenograft model, UM-PEL-1, by transferring freshly-isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth. We utilized this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. Transcriptome analysis by genomic arrays revealed that bortezomib downregulated cell cycle progression, DNA replication, and Myc-target genes.
Publication Title
Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
OSM increases the antiviral effect of IFN in Huh7 cells infected with hepatitis A virus (HAV) or HCV replicon and synergizes with IFN in the induction of antiviral genes
Publication Title
Oncostatin M enhances the antiviral effects of type I interferon and activates immunostimulatory functions in liver epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In seed plants, leaves are born on radial shoots but unlike shoots they are determinate dorsiventral organs made of flat lamina. YABBY genes are found only in seed plants and in all cases studied, are expressed primarily in lateral organs and in a polar manner. Despite their simple expression, Arabidopsis plants lacking all YABBY gene activities have a wide range of morphological defects in all lateral organs as well as the shoot apical meristem. Here we show that leaves lacking all YABBY activities are initiated as dorsiventral appendages but fail to properly activate lamina programs. In particular, the activation of most CIN-TCPs does not commence, SAM-specific programs are reactivated, and a marginal leaf domain is not established. Altered distribution of auxin signalling and the auxin efflux carrier PIN1, highly reduced venation, initiation of multiple cotyledons, and gradual loss of the SAM accompany these defects. We suggest that YABBY functions were recruited to mould modified shoot systems into flat plant appendages by translating organ polarity into lamina specific programs that include marginal auxin flow and activation a maturation schedule directing determinate growth.
Publication Title
Differentiating Arabidopsis shoots from leaves by combined YABBY activities.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
In Drosophila, fibrillar flight muscles (IFMs) enable flight, while tubular muscles mediate other body movements. Here, we use RNA-sequencing and isoform-specific reporters to show that spalt major (salm) determines fibrillar muscle physiology by regulating transcription and alternative splicing of a large set of sarcomeric proteins. We identify the RNA binding protein Arrest (Aret, Bruno) as downstream of salm. Aret shuttles between cytoplasm and nuclei, and is essential for myofibril maturation and sarcomere growth of IFMs. Molecularly, Aret regulates IFM-specific transcription and splicing of various sarcomeric targets, including Stretchin and wupA (TnI), and thus maintains muscle fiber integrity. As Aret and its sarcomeric targets are evolutionarily conserved, similar principles may regulate mammalian muscle morphogenesis. Overall design: 9 samples from Drosophila melanogaster were analyzed in duplicate: control dissected wildtype flight muscle at 30h APF, 72h APF and 0 day adult, jump muscle and whole leg from 1d adult and RNAi/mutant conditions for salm (1d flight muscle) and aret (30h, 72h and 1d flight muscle)
Publication Title
The RNA-binding protein Arrest (Bruno) regulates alternative splicing to enable myofibril maturation in Drosophila flight muscle.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Vaccination induces immunostimulatory signals which are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Thus, here we characterized IL-10-producing cells treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1. These IL-10+ DC showed impaired in vitro T-cell stimulatory capacity, which was rescued by incubation with IL-10R and PD-L1-inhibiting antibodies.
Publication Title
IL-10 expression defines an immunosuppressive dendritic cell population induced by antitumor therapeutic vaccination.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Mouse ES cells were stably transduced with a lentivirus expressing either wild-type KBP or the stable mutant KBP(KK/RR) and maintained in self-renewing growth conditions. RNA-seq was performed to assess mRNA expression differences caused by the stabilization of KBP. Overall design: 6 samples [a triplicate set for ES cells expressing wild-type KBP and a triplicate set expressing KBP(KK/RR)] were analyzed.
Publication Title
The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 213 Downloadable Samples
- NextSeq 500
Description
A specific subpopulation of neural progenitor cells, the basal radial glia cells (bRGCs) of the outer subventricular zone (OSVZ), are thought to have a key role in the evolutionary expansion of mammalian neocortex. In the developing lissencephalic mouse neocortex, bRGCs exist at low abundance and show significant molecular differences from bRGCs in developing gyrencephalic species. Here, we demonstrate that developing mouse medial neocortex, in contrast to the canonically studied lateral neocortex, exhibits an OSVZ and an abundance of bRGCs similar to that in developing gyrencephalic neocortex. Unlike bRGCs in developing mouse lateral neocortex, the bRGCs in medial neocortex exhibit human bRGC-like gene expression, including expression of Hopx, a human bRGC marker. Disruption of Hopx expression in mouse embryonic medial neocortex and forced Hopx expression in mouse embryonic lateral neocortex demonstrate that Hopx is required and sufficient, respectively, for a bRGC abundance as found in developing gyrencephalic neocortex. Taken together, our data identify a novel bRGC subpopulation in developing mouse medial neocortex that is highly related to bRGCs of developing gyrencephalic neocortex. Overall design: 221 single-cell transcriptomes from microdissected medial neocortex of E18.5 mouse embryos (two independent analyses using a pool of 8 neocortices each).
Publication Title
A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 175 Downloadable Samples
- Illumina HiSeq 2000
Description
Trascriptome analysis of osteosarcoma samples were performed Overall design: Tumor samples were obtained from a previously published Sleeping Beauty forward genetic screen, cell lines were derived from previous primary tumors and sequenced using Illumina HiSeq 2000
Publication Title
Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in Osteosarcoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HiSeq 4000
Description
The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. However, most siRNAs or shRNAs targeting either CD95 or CD95L induce DICE (Death Induced by CD95/CD95L Elimination), a form of cell death in which a combination of different cell death pathways are activated, that is selective for transformed cells, and that preferentially affects cancer stem cells. We now provide evidence that both CD95 and CD95L are part of a network of genes that contain sequences that when expressed as either siRNAs or shRNAs are toxic to cancer cells. They act through canonical RNAi by targeting the 3''UTRs of critical survival genes. We propose that these embedded toxic sequences are part of a conserved mechanism that regulates cell death, and we predict the existence of endogenous siRNAs, that when produced, induce cell death to regulate genome fidelity. Our data have implications for cancer therapy and the use of RNAi. Overall design: 293T (shL3 site deleted) cells were infected with either pTIP-shScr or pTIP-shL3 and following puromycin selection large RNAs were analyzed by deep sequencing 50 or 100hrs after addition of doxycycline/HeyA8 (shR6 site deleted) cells were infected with either pLKO-shScr or pLKO-shR6 and following puromycin selection large RNAs were analyzed by deep sequencing 50 or 100hrs after addition of selection.
Publication Title
Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples