PURPOSE: Hyperoxia is toxic to photoreceptors, and this toxicity may be important in the progress of retinal dystrophies. This microarray study examines gene expression induced in the C57BL/6J mouse retina by hyperoxia over the 14-day period during which photoreceptors first resist, then succumb to, hyperoxia. METHODS: Young adult C57BL/6J mice were exposed to hyperoxia (75% oxygen) for up to 14 days. On day 0 (control), day 3, day 7, and day 14, retinal RNA was extracted and processed on Affymetrix GeneChip Mouse Genome 430 2.0 arrays. Microarray data were analyzed using GCOS Version 1.4 and GeneSpring Version 7.3.1. RESULTS: The overall numbers of hyperoxia-regulated genes increased monotonically with exposure. Within that increase, however, a distinctive temporal pattern was apparent. At 3 days exposure, there was prominent upregulation of genes associated with neuroprotection. By day 14, these early-responsive genes were downregulated, and genes related to cell death were strongly expressed. At day 7, the regulation of these genes was mixed, indicating a possible transition period from stability at day 3 to degeneration at day 14. CONCLUSIONS: Microarray analysis of the response of the retina to prolonged hyperoxia demonstrated a temporal pattern involving early neuroprotection and later cell death, and provided insight into the mechanisms involved in the two phases of response. As hyperoxia is a consistent feature of the late stages of photoreceptor degenerations, understanding the mechanisms of oxygen toxicity may be important therapeutically.
Gene regulation induced in the C57BL/6J mouse retina by hyperoxia: a temporal microarray study.
Specimen partView Samples
The retinas of simian primates include a specialized, cone-rich, macula which regards the central visual field and mediates high acuity and colour vision. A prominent feature of the macula is the fovea centralis - a 1 mm-wide, avascular depression in the inner retinal surface that corresponds with a local absence of rods and a peak spatial density of cones in the outer photoreceptor layer. The arrangement of macular photoreceptors, and their specialized midget circuits, are the neural substrate for high resolution vision in primates. Macular-specific photoreceptor loss and abnormal blood vessel growth within the macula are the major causes of untreatable vision loss worldwide. However, the genes that regulate specialization of the macula, and the causes of its vulnerability to degeneration, remain obscure. Microarrays were used to compare gene expression between macula and non-macular regions during a critical phase of human retinal vascular development.
Differential expression of anti-angiogenic factors and guidance genes in the developing macula.
Specimen partView Samples
Low-level infection is believed to play a role in the degradation of the outer blood retinal barrier, which is composed of retinal pigment epithelial (RPE) cells.
Microarray analysis of gene expression in West Nile virus-infected human retinal pigment epithelium.
Sex, Specimen part, Disease, Disease stage, Cell lineView Samples
Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs, especially in older people. Although these drugs are usually considered safe, recent evidence suggests that high dose and/or long term use of PPIs may have several detrimental effects, including increased risk of adverse cardiovascular events. The impact of PPI in the aging host environment still need to be characterized. Aged tissues, including vascular tissues, accumulate senescent cells that can communicate with their environment by secreting a myriad of cytokines and growth factors. Human coronary artery endothelial cells (HCAECs) provide an excellent model system to study in vitro most aspects of cardiovascular function and disease related to cellular senescence. The purpose of this study is thus to investigate the in vitro effects of two well-known PPIs (Omeprazole and Lansoprazole) on endothelial gene expression in senescent e non-senescent HCAECs.
Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment.
CD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN- and TNF-. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration.
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Specimen part, TimeView Samples
Autism spectrum disorder (ASD) is a disorder of brain development believed, in most cases, to be of genetic origin. We use induced pluripotent stem cells (iPSCs)-derived 3-dimensional neural cultures (organoids) in patients with ASD and macrocephaly to investigate neurodevelopmental alterations that cause this form of ASD. By using transcriptome analyses, we identified modules of co-expressed genes significantly upregulated in ASD patients compared to non-ASD first-degree family members. Overall design: Total RNA was prepared from terminal differentiation day 0, 11 and 31 of iPSCs-derived neural cultures from ASD patients and non-ASD first-degree family members. A total of 4 patients and 8 controls (unaffected family members) were analyzed in replicates (two to three iPSC clones per person).
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders.
No sample metadata fieldsView Samples
CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear.
Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection.
Specimen part, TimeView Samples
The entorhinal cortex of the mouse seems to be sensitive to molecular mechanisms that have been linked to the pathology of Alzheimer's disease. In this microarray study we are interested in comparing the expression profile of the left versus the right EC of the mouse, in order to understand if there is a significant difference in gene expression that might reveal any insights into the differential activation of these areas.
Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease.
Age, Specimen partView Samples
As exposure to episodic drought can impinge significantly on forest health and the establishment of productive tree plantations, there is great interest in understanding the mechanisms of drought response in trees. The ecologically dominant and economically important genus Populus, with its sequenced genome, provides an ideal opportunity to examine transcriptome level changes in trees in response to a drought stimulus. The transcriptome level drought response of two commercially important hybrid Populus clones (P. deltoides P. nigra, DN34, and P. nigra P. maximowiczii, NM6) was characterized over a diurnal period using a 4 2 2 completely randomized factorial ANOVA experimental design (four time points, two genotypes, and two treatment conditions) using Affymetrix Poplar GeneChip microarrays. Notably, the specific genes that exhibited changes in transcript abundance in response to drought differed between the genotypes and/or the time of day that they exhibited their greatest differences. This study emphasizes the fact that it is not possible to draw simple, generalized conclusions about the drought response of the genus Populus on the basis of one species, nor on the basis of results collected at a single time point. The data derived from our studies provide insights into the variety of genetic mechanisms underpinning the Populus drought response, and provide candidates for future experiments aimed at understanding this response across this economically and ecologically important genus.
Genotype and time of day shape the Populus drought response.
Age, Specimen part, TreatmentView Samples
Two colon cancer cell lines are under study. SW480 and SW620. The first one is derived from primary cancer, SW620 are from lymphnode metastatic sites. they both comes from the sampe patient. Polisomal RNA fractions from the two isogenic colon cancer cells lines was purified by sucrose gradient and hybridized on affymetrix hgu133a chips. this study is complementary to the series GSE1323 were total RNA was used instead. Comparison between the polysomal fraction chips and the total RNA chips is performed and the analysis proposed in a paper from the authors (at the moment in preparation).
Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis.
No sample metadata fieldsView Samples