Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme endonuclease VIII-like 3 (NEIL3) was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 following MI in mice, especially in a fibroblast-enriched cell fraction. Neil3-/- mice showed increased mortality after MI compared to WT, caused by myocardial rupture. Neil3-/- hearts displayed enrichment of mutations in genes involved in mitogenesis of fibroblasts and transcriptome analysis revealed dysregulated fibrosis. Correspondingly, proliferation of vimentin+ and aSMA+ (myo)fibroblasts was increased in Neil3-/- hearts following MI. We propose that NEIL3 operates in genomic regions crucial for regulation of cardiac fibroblast proliferation and thereby controls extracellular matrix modulation after MI. Overall design: RNA from infarcted and non-infarcted LV of WT and Neil3-/- C57BL/6 mice obtained three days after induced myocardial infarction were subjected to RNA sequencing using Illumina Hiseq 2000
NEIL3-Dependent Regulation of Cardiac Fibroblast Proliferation Prevents Myocardial Rupture.
Age, Specimen part, Cell line, Subject
View SamplesThe goal of the microarray experiment was to identify genes that were differentially expressed in NAD-treated and water-treated sweet orange leaf tissues. Results indicated that, compared with the water treatment, the NAD tretament triggered profound transcriptome changes in the citrus leaves, with about 1,200 genes being up-regulated or down-regulated by twofold or more.
Exogenous Nicotinamide Adenine Dinucleotide Induces Resistance to Citrus Canker in Citrus.
Specimen part, Time
View SamplesWe have discovered a small subpopulation of virus-specific CD8 T-cells that sustains the T-cell response in chronic infections. These cells are defined by - and depend on - the expression of the transcription factor Tcf1 (T cell factor 1) and show key characteristics of central memory cells while lacking an effector signature. Unlike conventional memory cells, Tcf1+ T-cells display hallmarks of an “exhausted” phenotype, including the expression of certain inhibitory receptors. Overall design: Naive Tcf1-GFP+ P14 cells (Naive) were transferred into Vb5 recipient mice (CD45.1) prior to infection with LCMV clone 13 (c13). Tcf1-GFP+ P14 cells (chronic Tcf1+) and Tcf1-GFP- P14 cells (chronic Tcf1-) were flow sorted on day 28 post infection. Naive Tcf1-GFP+ P14 cells (Naive) were also transferred into C57BL/6 hosts (CD45.1.2) prior to infection with LCMV Armstrong (Arm). Tcf1-GFP+ P14 cells (memory Tcf1+) and Tcf1-GFP- P14 cells (memory Tcf1-) were flow sorted on day 28 post infection. Total RNA was extracted, cDNA libraries prepared and sequencing was performed using Illumina HiSeq 2500 technology.
T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.
Specimen part, Cell line, Subject
View SamplesComparison between APPPS1-FVB and APPPS1-FVBxABCC1ko mice
Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice.
Specimen part
View SamplesInfection is a major complication and cause of mortality and morbidity after acute stroke however the mechanisms are poorly understood. After experimental stroke the microarchitecture and cellular composition of the spleen are extensively disrupted resulting in deficits to immune function.
Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages.
Specimen part, Treatment
View SamplesGenome-wide alternative splice analysis of RNA from lupus and its severe form lupus nephritis
Genome-wide peripheral blood transcriptome analysis of Arab female lupus and lupus nephritis.
Sex, Specimen part, Disease stage
View SamplesLMO2 is a component of multisubunit DNA-binding transcription factor complexes that regulate gene expression in hematopoietic stem and progenitor cell development. Enforced expression of LMO2 causes leukemia by inducing hematopoietic stem cell-like features in T-cell progenitor cells, but the biochemical mechanisms of LMO2 function have not been fully elucidated. In this study we systematically dissected the LMO2/LDB1 binding interface to investigate the role of this interaction in T-cell leukemia. Alanine scanning mutagenesis of the LIM interaction domain of LDB1 revealed a discrete motif R320LITR required for LMO2 binding. Most strikingly, co-expression of full length, wild type LDB1 increased LMO2 steady state abundance, whereas co-expression of mutant proteins deficient in LMO2 binding compromised LMO2 stability. These mutant LDB1 proteins also exerted dominant negative effects on growth and transcription in diverse leukemic cell lines. Raw gene expression data on HSB-2 cells is presented here. Overall design: RNAseq were performed on HSB cell lines to examine their expression patterns
LMO2 Oncoprotein Stability in T-Cell Leukemia Requires Direct LDB1 Binding.
No sample metadata fields
View SamplesEnzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA.
Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer.
Specimen part, Cell line
View SamplesADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in the CNC. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein.
Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.
Specimen part
View SamplesWe aim to identify genes differentially expressed between mouse WT and COUP-TFI_Nex-Cre mutant cortices.
Postmitotic control of sensory area specification during neocortical development.
Specimen part
View Samples