We report XBP1 activation and regulation of pro-inflammatory signaling in astrocytes, microglia, and CNS-recruited pro-inflammatory monocytes during EAE. Overall design: Analysis of RNA expression in astrocytes, microglia, and monocytes sorted by flow cytometry. Mice transduced with astrocyte-targeting lentiviruses encoding non-targeting or Xbp1-targeting shRNAs.
Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation.
Sex, Disease, Cell line, Subject
View SamplesTo identify genes regulated by Rx3 during optic vesicle morphogenesis, adult zebrafish carriers of a null rx3 mutation were mated. Before 13 hours post fertilization (hpf), the earliest time point at which optic vesicle evagination phenotypes could be reliably detected, offspring were phenotypically separated into pools comprising of mutants with an absence of optic vesicles or siblings exhibiting a wild-type phenotype. Three replicates of pooled RNA samples from 13 hpf eyeless mutants (rx3-/-) or phenotypically wild-type siblings (rx3+/+ or rx3+/-), and one replicate of 13 hpf wild-type zebrafish larva were collected for whole transcriptome sequencing. Overall design: Whole transcriptome sequencing (RNA-seq) was performed on zebrafish rx3-/- mutants, wild-type siblings and wild-type AB strains at 13 hpf
Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis.
No sample metadata fields
View SamplesTCDD increased expression of numerous differentiation specific genes and decreased expression of numerous genes involved in mitochondrial health and redox homeostasis
2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation.
Specimen part, Cell line
View SamplesObjective: The etiology of PCOS is mostly unknown. Existing data support both genetic and environmental factors in its pathogenesis. Design: Prospective case - control study. Setting: University Hospital. Patients: 25 patients undergoing IVF-ICSI treatment. Intervention: Genome-wide oligonucleotide microarray technology was used to study differential gene-expression patterns of cultured human cumulus cells from IVF patients divided into 4 groups according to disease state (PCOS vs. Control) and BMI (Obese vs. Lean). Results: Two differential PCOS gene expression profiles were established: Lean-Type was formed by comparing PCOS lean (PL) vs. non-PCOS lean (NL) individuals; Obese-Type was formed by comparing PCOS obese (PO) vs. non-PCOS (NO) obese patients. Conclusions: Different molecular pathways are associated with PCOS in Lean and Obese individuals, as demonstrated by gene expression profiling of cumulus cells. Our findings provide insights into the molecular pathogenesis of PCOS.
Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients.
Sex
View SamplesConcentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to twelve weeks.
Concentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to 12 weeks.
Sex, Age, Specimen part, Subject
View SamplesDevelopmental programming is the concept that environmental factors, particularly during foetal life, can alter development, metabolism and physiology of an organism and this can have consequences later in life. There is growing interest in developmental programming in livestock species, particularly effects of maternal pregnancy nutrition, which is easy to manipulate. Recent research, using a sheep model, has shown that milk production in ewe offspring may be susceptible to maternal nutritional programming, such that over nutrition (ad libitum) of the pregnant dam, compared with maintenance nutrition, may impair their first lactation performance and result in the weaning of lighter lambs. RNA-seq was performed to identify gene expression differences as a result of maternal nutrition in ewe offspring during their first parity. Samples were collected in late pregnancy and during lactation, allowing us to examine gene expression changes during maturation of the ovine mammary gland. Overall design: Three biological replicates were sequenced for each of the treatment conditions (maternal nutrition: sub-maintenance, maintenance, and ad libitum) and time points (late pregnancy and lactation). Each biological replicate consisted of RNA from multiple individuals (late pregnancy n=3, lactation n=2).
Functional development of the adult ovine mammary gland--insights from gene expression profiling.
Specimen part, Subject
View SamplesEight week old female C57BL/6 mice were exposed to arsenate in drinking water (50 ppm) for a period of twelve weeks (n = 5). Control animals received distilled deionized water (n = 5). Lung tissue was dissected and used for RNA isolation and gene expression microarray analysis.
Genome-wide analysis of DNA methylation and gene expression changes in the mouse lung following subchronic arsenate exposure.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesA complex network of inflammation succeeds somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. To date, no model exists to allow us to study the underlying mechanisms that govern the initial phase of the immune response as cells are transformed to become the precursors of cancer. Here we describe the development of an innovative double binary animal model designed in zebrafish for exploring regulatory programming of the myeloid cells as they respond to oncogenic transformed melanocytes. This modular system harnesses the power of zebrafish genetics. For studies of melanocyte transformation we generated a hormone-inducible binary system allowing for temporal control of different Ras-oncogene (NRasK61Q, HRasG12V, KRasG12V) expression in melanocytes allowing us to truly study melanoma initiation. This binary model was then coupled to a model for regulatory profiling of the active transcriptome of macrophages and neutrophils which is based on the in vivo biotinylation of nuclei and their subsequent isolation by streptavidin affinity purification. For the first time regulatory profiling of neutrophils as they respond to the earliest precursors of melanoma, revealed a number of factors upregulated in neutrophils that may promote progression to melanoma including fgf1, fgf6, cathepsin H, cathepsin L, galectin 1 and galectin 3. Overall design: We report the design of a double binary approach in zebrafish to study the neutrophil response to transformed melanocytes. By coupling a novel inducible model for melanocyte transformation to a model for the in vivo biotinylation of neutrophil nuclei we can isolate the neutrophil nuclei directly from the in vivo context allowing for RNA-seq analysis of the active transcriptome.
Generation of a double binary transgenic zebrafish model to study myeloid gene regulation in response to oncogene activation in melanocytes.
Specimen part, Cell line, Treatment, Subject
View SamplesContext: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive- aged women, is associated with systemic low-grade inflammation. Objective: We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients. Design: Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines. Setting: This was a university-based study. Patients: Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files. Interventions:GCcytokine/chemokinemRNAswere identified and analyzed by gene-chip microarrays/ qPCR before and after culture withhumanchorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed. Main Outcome Measures: Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index. Results: The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production. Conclusions: Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype.
Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome.
Specimen part
View SamplesUnderstanding distinct gene expression patterns of normal adult and developing fetal human pancreatic a and b cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase b cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify a, b, and d cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the sub-populations by flow cytometry and, using next generation RNA sequencing, we report on the detailed transcriptomes of fetal and adult a and b cells. We observed that human islet composition was not influenced by age, gender, or body mass index and transcripts for inflammatory gene products were noted in fetal b cells. In addition, within highly purified adult glucagon-expressing a cells, we observed surprisingly high insulin mRNA expression, but not insulin protein expression. This transcriptome analysis from highly purified islet a and b cell subsets from fetal and adult pancreata offers clear implications for strategies that seek to increase insulin expression in type 1 and type 2 diabetes. Overall design: RNA-sequencing of highly purified human adult and fetal islet cell subset was performed using our newly developed method. Using this data, we can study and compare the detailed transcriptome or alpha and beta cells during development.
Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.
No sample metadata fields
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