The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity.
Human TCR-alpha beta+ CD4- CD8- T cells can derive from CD8+ T cells and display an inflammatory effector phenotype.
Specimen part
View SamplesA transgenic mouse was generated using a CD2-driven transgene containing the cDNA of Ppp2ca to achieve over-expression of PP2Ac in T cells. Nave CD4 T cells were isolated and lysed at times 0, 6, and 24 hours after stimulation with anti-CD3 and anti-CD28
Protein phosphatase 2A enables expression of interleukin 17 (IL-17) through chromatin remodeling.
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View SamplesUOK257 cell line was derived from a BHD patient. It harbors a germline mutation in FLCN (c.1285dupC) and LOH. UOK257-2 cells were generated from UOK257 cells by introducing wildtype FLCN using retrovirus. FLCN inactivation induces TFE3 transcriptional activity by increasing its nuclear localization. Thus expression microarray was used to identify the genes regulated by FLCN and TFE3.
The UOK 257 cell line: a novel model for studies of the human Birt-Hogg-Dubé gene pathway.
Cell line
View SamplesCaloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling
Caloric restriction in leptin deficiency does not correct myocardial steatosis: failure to normalize PPAR{alpha}/PGC1{alpha} and thermogenic glycerolipid/fatty acid cycling.
Specimen part
View SamplesIsolated methylmalonic acidemia (MMA) is a pleiotropic enzymatic defect of branched-chain amino acid oxidation most commonly caused by deficiency of methylmalonyl-CoA mutase (MUT). End stage renal disease (ESRD) is emerging as an inevitable disease-related complication, recalcitrant to conventional therapies and liver transplantation. To establish a viable model of MMA-associated renal disease, methylmalonyl-CoA mutase (Mut) was expressed in the liver of Mut -/- mice as a stable transgene under the control of an albumin (INS-Alb-Mut) promoter. Mut -/- ;TgINS-Alb-Mut mice were rescued from the neonatal lethality displayed by Mut -/- mice and manifested a decreased glomerular filtration rate (GFR), chronic tubulointerstital nephritis (CTIN) and prominent ultrastructural changes in the proximal tubular mitochondria, replicating precisely the renal manifestations seen in a large MMA patient cohort.
Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia.
Sex, Specimen part
View SamplesComparison of treatment sensitive GSC clones (TSGC) with treatment resistant GSC clones (TRGC). We used microarrays to identify molecular signatures of TRGC (upregulated genes).
Protective properties of radio-chemoresistant glioblastoma stem cell clones are associated with metabolic adaptation to reduced glucose dependence.
Specimen part
View SamplesComparison of parental GSC (GSC-parental) with treatment resistant GSC clones survived 500uM TMZ treatment (GSC-500uM TMZ)
Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.
Cell line, Treatment
View SamplesWe report the application of RNA-seq analysis for high-throughput profiling of murine lungs infected with Aspergillus fumigatus. We compared the lung transcription of wildtype murine lungs and lungs from mice deficient in metabolic cytokine adiponectin. Overall design: Examination of 2 different mice strain and comparison of lung transcripts in response to Aspergillus fumigatus infection.
The Metabolic Cytokine Adiponectin Inhibits Inflammatory Lung Pathology in Invasive Aspergillosis.
Specimen part, Cell line, Subject
View SamplesLipotoxicity is a metabolic disorder that results from accumulation of lipids, particularly fatty acids, in non-adipose tissue leading to cellular dysfunction, lipid droplet formation, and cell death. Our studies indicate for the first time that the neurovascular circulation also can manifest lipotoxicity, which could have major effects on cognitive function. The penetration of integrative systems biology approaches is limited in this area of research, which reduces our capacity to gain an objective insight into the signal transduction and regulation dynamics at a systems level.
A systems biology analysis of brain microvascular endothelial cell lipotoxicity.
Specimen part
View SamplesUnderstanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. Caenorhabditis elegans XX animals are hermaphrodites that exhaust their sperm after 3 d of egg-laying. Even though C. elegans can live for many days after cessation of egg-laying, the molecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism. To study the effects of sperm depletion and aging of C. elegans during the first 6 d of adulthood, we measured the transcriptomes of first-day adult hermaphrodites and sixth-day sperm-depleted adults, and, at the same time points, mutant fog-2(lf) worms that have a feminized germline phenotype. We found that we could separate the effects of biological aging from sperm depletion. For a large subset of genes, young adult fog-2(lf) animals had the same gene expression changes as sperm-depleted sixth-day wild-type hermaphrodites, and these genes did not change expression when fog-2(lf) females reached the sixth day of adulthood. Taken together, this indicates that changing sperm status causes a change in the internal state of the worm, which we call the female-like state. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm. Overall design: 4 conditions; 3 samples per condition. Young adults are 1d old adults without visible eggs. Aged adults are 6th day adults, post-egg-laying. The fog-2 mutant strain used was JK574
The <i>Caenorhabditis elegans</i> Female-Like State: Decoupling the Transcriptomic Effects of Aging and Sperm Status.
Cell line, Subject
View Samples