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SRP077214
Mus musculus
31 Downloadable Samples
Illumina HiSeq 2000
Description
Microcephaly and medulloblastoma result from mutations that compromise genomic stability. We report that Atr, which is mutated in the microcephalic disorder Seckel syndrome, is required to maintain chromosomal integrity during postnatal cerebellar neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis, and cerebellar hypoplasia. Co-deletions of either Bax and Bak or p53 prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. Atr-deficient CGNPs showed impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to Atr-deficient proliferation was p53-driven. Acute Atr inhibition in vivo by nanoparticle-formulated VE-822 reproduced the disruptions seen with Atr deletion. Our data show that p53-driven apoptosis and senescence, and non-apoptotic cell death redundantly limit growth in Atr-deficient progenitors. These overlapping mechanisms that suppress growth in Atr-disrupted CGNPs may be exploited for treatment of CGNP-derived medulloblastoma using Atr inhibition. Overall design: RNA-Seq on total RNA from P3 mouse cerebella of Math1-Cre;Atr-loxP/loxP;Bax-loxP/loxP;Bak--/- (n=5), Math1-Cre;Bax-loxP/loxP;Bak--/- (n=4), Math1-Cre;Atr-loxP/loxP;p53-loxP/loxP (n=5), and Math1-Cre;p53-loxP/loxP (n=3), all run in 2 lanes
Publication Title
ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 191 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide association studies (GWAS) have been pivotal to increasing our understanding of intestinal disease. However, the mode by which genetic variation results in phenotypic change remains largely unknown, with many associated polymorphisms likely to modulate gene expression. Analyses of expression quantitative trait loci (eQTL) to date indicate that as many as 50% of these are tissue specific. Here we report a comprehensive eQTL scan of intestinal tissue.
Publication Title
Expression quantitative trait loci analysis identifies associations between genotype and gene expression in human intestine.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
T cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+TCRV+ restricted cytotoxic T cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report the presence of CTL clones with varying TCRV repertoire in 70% of patients with Waldenstroms Macroglobulinaemia (WM) (n=20). Previous nucleoside analogue (NA) therapy, associated with an increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRV expansions (X2=11.6; P<0.001) as 83% of patients without (n=6) and only 7% with TCRV expansions (n=14) had received NA. Clonality of CD3+CD8+CD57+TCRV+ restricted CTLs were confirmed by TCRV CDR3 size analysis and direct sequencing. To characterize CTL clones, samples of CD3+CD8+CD57+TCRV+ cells were profiled using DNA microarrays and the results were validated on both gene and protein level. By gene set enrichment analysis, CTL clones not only expressed genes (GZMB, PRF1, FGFBP2) from cytotoxic pathways but also genes which suppress apoptosis, inhibit proliferation, arrest cell cycle G1/S transition and activate T cells (RAS, CSK and TOB pathways). Proliferation tracking confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity and anergic nature of clonal T cells in a B cell tumor.
Publication Title
Clonal expansions of cytotoxic T cells exist in the blood of patients with Waldenstrom macroglobulinemia but exhibit anergic properties and are eliminated by nucleoside analogue therapy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In this study we applied genomic profiling to evaluate the transcriptomic differences between murine models ot atopic dermatitis.
Publication Title
Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Tumor necrosis factor receptor associated factor 6 (TRAF6) is an adaptor protein that regulates NF-B and MAPK signaling pathway and is reported to affect immune response and cell death in immune cells. However, the roles of TRAF6 in epithelium have not been well investigated. Using a mouse model of imiquimod-induced psoriasis dermatitis, we show that TRAF6 in epithelial cells totally regulates IL-17-mediated inflammation in the skin. Mice lacking TRAF6 in keratinocytes were unable to activate dendritic cells and failed to produce IL-23 or initiate IL-17 production from T cells at the imiquimod-treated sites. Subcutaneous administrations of IL-23 restored IL-17 production in the mutant animals, suggesting that the induction of IL-23 production is the major TRAF6-dependent contribution of keratinocytes to this process. Therefore, the epithelial TRAF6 signaling is supposed to play an essential role in instructing and propagating the cutaneous immune response.
Publication Title
Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Synthetic transcription factors can be applied to many areas of biotechnology, medicine, and basic research. Currently, the most common method for engineering synthetic transcription factors has been based on programmable DNA-binding domains of zinc finger proteins, Transcription Activator-Like Effectors (TALEs), and most recently the CRISPR/Cas9 system. These transcription factor platforms consist of the DNA-binding domain fused to potent transcriptional activation domains, most commonly the tetramer of the minimal transactivation domain of the VP16 protein from herpes simplex virus, referred to as VP64. Although many applications are well-suited for the targeted activation of a single gene, genetic reprogramming requires the coordinated regulation of many nodes of natural gene networks as is typically performed by naturally occurring reprogramming factors. Thus we sought to combine principles from each of these approaches by attaching potent transcriptional activation domains to a natural reprogramming factor to increase the efficiency and/or rate of cell fate conversion. In this study, we evaluated the effects of fusing potent activation domains to the transcription factor MyoD, the master regulator of the skeletal myoblast lineage. In certain non-myogenic lineages, MyoD overexpression causes upregulation of the myogenic gene network and conversion to a myoblast phenotype including cell fusion into multinucleated myotubes. Compared to wild-type MyoD, the VP64-MyoD fusion protein induced greater overall reprogramming of global gene expression. This simple approach for increasing the potency of natural reprogramming factors circumvents the need for screening engineered proteins and leads to a more robust cellular reprogramming compared to treatment with the wild type transcription factor. Overall design: Human dermal fibroblasts were transduced with a single tet inducible lentivirus that expresses either WT-MyoD or VP64-MyoD in response to treatment with doxycycline. Untreated human dermal fibroblast served as the negative control. Gene expression was measured using mRNA-seq, and differential expression was calculated using DESeq. All experiments were performed in biological duplicates.
Publication Title
Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Although corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy.
Publication Title
Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 1500
Description
Purpose: We found that IFN-g and IL-27 had suppressive effects on ILC2s cultured with IL-33. The goal of this study is to clarify the expressions of RNA induced by IFN-g and IL-27 in ILC2s. Methods: ILC2s were isolated from fat-asociated lymphid clusters (FALC) of wild-type mice. They were cultured with IL-33 (10ng/ml), IL-33 + IFN-g (10ng/ml), or IL-33 + IL-27 (10ng/ml) for 48hrs. RNA was isolated by Allprep DNA/RNA Micro Kit (QIAGEN), and cDNA libraries were prepared by TruSeq RNA Sample Preparation kits v2 (Illumina) according to the manufacturer’s low sample protocol. A HiSeq 1500 system (Illumina) was used for 50 single-end bases (50SE) sequencing. Results: Sequenced reads were trimmed for adaptor sequence, and masked for low-complexity or low-quality sequence, then mapped to the reference genome (mm9) using Bowtie2 v2.1.0 and TopHat2 v2.0.8. The transcript abundances were estimated as FPKM (fragments per kilobase of exon million fragments mapped) value using Cufflinks v2.1.1. We found that both IL-27 and IFN-g upregulated the expression of STAT1 and IRF1 which are regulated downstream of IFN-g receptor signaling, but there was no difference in the expression of GATA3, a critical transcription factor for ILC2 functions. Conclusions: Our study represents the detailed differences of RNA expressions by RNA-seq technology. Overall design: RNA-Seq analysis of ILC2s cultured with IL-33 (10ng/ml), IL-33 + IFN-g (10ng/ml), or IL-33 + IL-27 (10ng/ml) for 48hrs.
Publication Title
Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Loss of the interactions between lymphotoxin and its receptor was associated with MZM apoptotic cell clearance defects in BXD2 mice whereas loss of IFNAR in BXD2 mice normalized the function of MZMs. The analysis also intended to use MZMs isolated from BXD2-Ifnar-/- mice and BXD2 mice treated with sLTbR-Fc to identify the common pathways regulating the MZM function in these mice.
Publication Title
Interferon-induced mechanosensing defects impede apoptotic cell clearance in lupus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Goal: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those related to exosomes.
Publication Title
Differential gene expression of soluble CD8+ T-cell mediated suppression of HIV replication in three older children.
Sample Metadata Fields
Sex, Specimen part
View Samples