IMP3 (IGF2-mRNA binding protein 3) is a member of a family of IGF2-mRNA binding proteins that function in RNA stabilization, trafficking and localization. It exhibits the properties of an oncofetal protein and its expression correlates with the aggressive behavior of many tumors. In breast cancer, IMP3 is associated with the highly aggressive triple-negative subtype (TNBC) The challenge is to identify specific proteins and functions that are regulated by IMP3. As an approach to this problem, we compared the mRNA expression profile of SUM-1315 cells, a TNBC cell line, to the same cells that had been depleted of IMP3. Overall design: SUM-1315 breast cancer cells were were infected with lentivirus for control shRNA and two different IMP3 shRNAs and processed for RNA-sequencing
IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer.
Specimen part, Subject
View SamplesThe goal of this study was to compare mRNA from mammary epithelial cells of 3 mammary-specific Nmi knockout FVB with corresponding wildtype control. This was performed to obtain clues to the signaling pathways that were impacted in the mammary epithelial cells upon knocking-out Nmi expression. Overall design: To determine how the loss of Nmi contributed to a hyper-proliferative phenotype during puberty and lactation, we performed global RNAseq analysis from enriched mammary epithelial organoids from lactation day1 (L1), the time when Nmi protein expression in normal mammary epithelium is at its highest level. We compared 2 groups with 3 mice/group. We used second and third mammary glands of each mouse. These glands were isolated from mice on the first day of lactation, minced and dissociated in digestion medium (HBSS containing collagenase I (Sigma Aldrich, St. Louis, MO) (1mg/mL) and Pronase (Sigma Aldrich) (0.1mg/mL)) for two hours at 37C with shaking. Epithelial organoids were washed in PBS and enriched by pulse centrifugation to 1500rpm at least three times before subsequent assays.
Conditional knockout of N-Myc and STAT interactor disrupts normal mammary development and enhances metastatic ability of mammary tumors.
Specimen part, Subject
View SamplesDespite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and of its proteolytic fragments are still poorly understood. The secreted APPs ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The -secretase generated APP intracellular domain, AICD, functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial. Previously, we have generated APPs knockin (KI) mice expressing solely the secreted ectodomain APPs. Here, we generated double mutants (APPs-DM) by crossing APPs-KI mice onto an APLP2-deficient background and show that APPs rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPs-DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP. To gain further mechanistic insight into which domains/proteolytic fragments are crucial for hippocampal APP/APLP2 mediated functions, we performed a DNA microarray transcriptome profiling of prefrontal cortex and hippocampus of adult APLP2-KO (APLP2-/-) and APPs-DM mice (APP/APLP2-/- mice).Interestingly, this analysis failed to reveal major genotype-related transcriptional differences. Expression differences between cortex and hippocampus were, however, readily detectable.
APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP.
Sex, Specimen part
View SamplesMicroarry from Treg with conditional knockout of Usp7
Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity.
Specimen part
View SamplesMetastatic melanoma is a deadly disease while non-metastatic melanoma and other cutaneous tumor types are usually cured with surgical removal of the primary tumors. This study evaluated gene expresion to determine if gene expression differences existed which would allow one to identify the metastatic tumors based on the expression of specific genes.
The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis.
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View SamplesNatural killer T (NKT) cells have immune stimulatory or inhibitory effects on the immune response that are context-dependent. This may be attributed in part to the existence of functional NKT cell subsets; however, these functional subsets have only been characterized on the basis of differential expression of a few transcription factors and cell surface molecules. Here we have analyzed purified populations of thymic NKT cell subsets at both the transcriptomic and epigenomic levels, and by single-cell RNA sequencing. Our data indicate that despite their similar antigen specificity, the functional NKT cell subsets are highly divergent populations characterized by many gene expression and epigenetic differences. Therefore the thymus imprints innate-like NKT cells with novel combinations of properties, including differences in proliferative capacity, homing, and effector functions that were not previously anticipated. Overall design: Analysis of single cell transcriptomic heterogeneity in mouse Va14 iNKT thymocyte subsets (NKT1, NKT2, NKT17 and NKT0). Samples were generated from individual experiment using a pool of thymocytes prepared from five five-week old C57BL/6J females. NKT cells subtypes were isolated from thymuses and directly sorted by flow cytometry into lysis buffer (96 well plate single cell sort). The preparation of samples occurred in 2 different batches (both having a equal representation of the different cell populations).
Innate-like functions of natural killer T cell subsets result from highly divergent gene programs.
Sex, Age, Specimen part, Cell line, Subject
View Samples5 strains of rat, WKY, spontaneously hypertensive rat (SHR) and 3 reciprocal congenic strains (WconSA, SconSA and SISA) were used to generate expression data across the genome using the Affymetrix rat genome chip set comprising the 230 A and 230 B chips. 5 animals from each strain were used. Expression data was determined for 2 ages: 6 week and 24 week with whole kidney RNA.
Genetic dissection of a blood pressure quantitative trait locus on rat chromosome 1 and gene expression analysis identifies SPON1 as a novel candidate hypertension gene.
Age, Specimen part
View SamplesThe hemibiotrophic fungal pathogen Colletotrichum graminicola is the causal agent of anthracnose disease on maize stalks and leaves. After the formation of appressoria the host cell wall is penetrated by the conversion of appressorial turgor pressure into forceful ejection of a penetration peg. Subsequently, C. graminicola establishes biotrophic hyphae in the penetrated epidermis cell at around 36 hours post inoculation (hpi) until a switch of hyphal morphology and lifestyle takes place during the colonization of neighboring host cells at around 72 hpi. During the ensuing necrotrophic growth, dark necrotic lesions are formed that are visible as anthracnose symptoms. We used microarrays to detail the global programme of gene expression during the infection process of Colletotrichum graminicola in its host plant to get insight into the defense response of this compatible interaction and into the metabolic reprogramming needed to supply the fungus with nutrients.
Common Motifs in the Response of Cereal Primary Metabolism to Fungal Pathogens are not Based on Similar Transcriptional Reprogramming.
Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dual Roles of RNF2 in Melanoma Progression.
Specimen part, Cell line
View SamplesEpigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms.
Dual Roles of RNF2 in Melanoma Progression.
Specimen part, Cell line
View Samples