This SuperSeries is composed of the SubSeries listed below.
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
Sex
View SamplesA need exists for biomarkers in T1D that can 1) sensitively and specifically detect disease-related immune activity prior to, and independent of, measurement of auto-antibodies towards islet cell antigens; 2) define immunopathological mechanisms; and 3) monitor changes in the inflammatory state associated with disease progression or response to therapeutic intervention. In an effort to fill this gap, we have applied a novel bioassay to both human and BB rat T1D whereby the complex milieu of inflammatory mediators present in plasma can be indirectly detected through their ability to drive transcription in peripheral blood mononuclear cells (PBMCs) drawn from healthy, unrelated donors. The resultant gene expressions are comprehensively measured with a microarray. In our human studies, we find that plasma of recent-onset T1D patients induces expression of a pro-inflammatory signature consisting in part of many interleukin-1 (IL-1) regulated genes related to immunological activation and immunocyte chemotaxis compared to unrelated healthy controls. This signature has been found to resolve in long-standing T1D subjects (>10 years post-onset), thus associating it with active autoimmunity. Importantly, this signature has been detected in pre-onset samples of progressors to T1D years prior to onset and prior to development of auto-antibodies directed towards islet antigens.
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
Sex
View SamplesA need exists for biomarkers in T1D that can 1) sensitively and specifically detect disease-related immune activity prior to, and independent of, measurement of auto-antibodies towards islet cell antigens; 2) define immunopathological mechanisms; and 3) monitor changes in the inflammatory state associated with disease progression or response to therapeutic intervention. In an effort to fill this gap, we have applied a novel bioassay to both human and BB rat T1D whereby the complex milieu of inflammatory mediators present in plasma can be indirectly detected through their ability to drive transcription in peripheral blood mononuclear cells drawn from healthy, unrelated donors. The resultant gene expressions are comprehensively measured with a microarray. In our human studies, we find that plasma of recent-onset T1D patients induces expression of a pro-inflammatory signature consisting in part of many interleukin-1 (IL-1) regulated genes related to immunological activation and immunocyte chemotaxis compared to unrelated healthy controls. This signature has been found to resolve in long-standing T1D subjects (>10 years post-onset), thus associating it with active autoimmunity. Importantly, this signature has been detected in pre-onset samples of progressors to T1D years prior to onset and prior to development of auto-antibodies directed towards islet antigens.
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
No sample metadata fields
View SamplesRecent revelations into microRNA function suggest that microRNAs serve as a key player in a robust adaptive response against stress in animals through their fine-tuning capability in gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene mir-60 in the nematode C. elegans promotes adaptive response against oxidative stress; animals lacking mir-60 dramatically extend lifespan under a mild and long-term oxidative stress condition, while they do not increase resistance against a strong and transient oxidative stress exposure. We found that canonical stress responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in the xenobiotic metabolism and pathogen defense response are up-regulated by the mir-60 loss. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. Overall design: To identify genes that respond to the mir-60 loss, RNA expression profiles were examined between the mir-60 loss mutant (mir-60(n4947)) and its control animals using the high-throughput sequencing technology. In this study, we used spe-9(hc88), a temperature-sensitive sterile strain, which has been shown in previous studies to have a lifespan similar to wild-type and widely used in gene expression studies to reduce the effect of RNA contamination from younger progenies. Both spe-9 single and mir-60;spe-9 double mutant animals were cultured at a restrictive temperature 23.5 °C, and treated with paraquat 5 mM during adulthood for chronic oxidative stress. Total RNAs were purified at the following time points: Day 0 young adult for both spe-9 and mir-60;spe-9 (just before paraquat exposure); Day 7 for both spe-9 and mir-60;spe-9 (50% survival time for spe-9); Day 10 for mir-60;spe-9 (50% survival time for mir-60;spe-9). For Day 0 controls, total RNAs were isolated twice independently for biological replicates. cDNA libraries were made for these 7 samples with indexed adapters using TruSeq Stranded mRNA Sample Prep Kit (Illumina), and sequenced on 2 lanes of flow cells on the HiSeq 2000/2500 platform, eventually providing 14 sequencing samples.
An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in <i>C. elegans</i>.
Specimen part, Treatment, Subject, Time
View SamplesMicroarray analysis has been applied to the study of ALS in order to investigate gene expression in whole spinal cord homogenates of SOD1 G93A mice and human ALS cases, although the massive presence of glial cells and inflammatory factors has made it difficult to define which gene expression changes were motor neuron specific. Recently, laser capture microdissection (LCM), combined with microarray analysis, has allowed the identification of motor neuron specific changes in gene expression in human ALS cases.
Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS.
No sample metadata fields
View SamplesWe performed mRNA-seq from hand-dissected fat body tissue from 68hr (after egg laying, AEL) and 92hr AEL Drosophila melanogaster larvae. Fat body was dissected from wild-type (OrR) males and testes were removed. We examined gene expression genome-wide with particular focus on genes in the underreplicated regions in the fat body. Overall design: Sequencing of poly-A selected RNA from 68hr AEL and 92hr AEL wild-type (OrR) Drosophila melanogaster male larvae. Sequences analyzed by Illumina sequencing. Two biological replicates are included for each developmental sample.
Dynamic changes in ORC localization and replication fork progression during tissue differentiation.
Sex, Specimen part, Subject
View SamplesWe use DSN normalized RNA-seq to transcriptionally profile FACS sorted 16C ovarian follicle cells. These data provide insights into the developmental control of gene expression programmed gene amplificaton. Overall design: Follicle cells were isolated from whole ovaries by trypsinization and filtering and stained with Hoescht. 16C follicle cells were isolated by FACS sorting based on DNA content (Hoescht). RNA was extracted with TRIzol reagent and 100ng of total RNA and used to generate a total library. This library was then subjected to DSN normalization prior to Illumina based sequencing.
Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression.
Specimen part, Cell line, Subject
View SamplesA/J mice are genetically predisposed to spontaneous and/or chemically-induced lung tumors while C57BL/6J (B6) mice are resistant. This genetic disparity provides a unique scenario to identify molecular mechanisms associated with the lung response to welding fume at the transcriptome level.
Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.
Treatment
View SamplesFor victims of radiological accidents, rapid dose estimation and damage prediction are essential. Administering the gold-standard biodosimetry chromosome aberration assay requires highly skilled individuals and several days of labor; consequently, rapid turnaround is an important concern. Identification of new dose estimation markers and damage-predicting in vivo molecules to replace the chromosome aberration assay is crucial to improving the delivery time of medical treatment. Here, we investigated the applicability of mRNA levels using a mouse model. Female C57BL/6J mice were X-ray irradiated at various doses, and a DNA microarray was then performed to identify differentially expressed mRNAs in whole blood. The microarray analysis identified 14 radioresponsive mRNAs with more than fourfold differences by pattern matching in the expression at 24 h postirradiation. In particular, mRNA expression of Slfn4, Itgb5, Smim3, Tmem40, Litaf, Gp1bb and Cxx1c was significantly increased in a radiation-dose-dependent manner, as validated by reverse transcription quantitative polymerase chain reaction. We also performed an analysis using the cBioPortal for Cancer Genomics and found that the overall survival of ovarian adenocarcinoma patients with alterations in Smim3 and that of thymoma patients with alterations in Cxx1c had a worse prognosis than patients without these alterations. These findings suggest that the expression of several genes in whole blood was a sensitive and specific biomarker of radiation exposure and can be used as a rapid and reliable prospective molecular biomarker in radiological emergencies.
Identification of Radiation-Dose-Dependent Expressive Genes in Individuals Exposed to External Ionizing Radiation.
Sex, Age, Specimen part, Treatment
View SamplesRetinoic acid receptors (RARs) , , and heterodimerize with Retinoid X receptors (RXR) , , and and bind the cis-acting response elements known as RAREs to execute the biological functions of retinoic acid during mammalian development. RAR mediates the anti-proliferative and apoptotic effects of retinoids in certain tissues and cancer cells, such as melanoma and neuroblastoma cells. Furthermore, ablation of RAR enhanced the tumor incidence of Ras transformed keratinocytes and was associated with resistance to retinoid mediated growth arrest and apoptosis.
RARγ is essential for retinoic acid induced chromatin remodeling and transcriptional activation in embryonic stem cells.
Specimen part, Treatment, Time
View Samples