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Macaca mulatta
22 Downloadable Samples
Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Metabolic, mitochondrial and behavioral correlations with transcriptional profiles from the CA1 and DG hippocampal regions of young and aged rhesus macaque. Increasing evidence indicates that obesity correlates with impaired cognitive performance during normal aging and is a major risk factor for Alzheimers disease. However, little is known regarding how peripheral metabolic variables affect cellular pathways in brain regions important for memory. Brain inflammation, mitochondrial dysregulation, and altered transcriptional regulation have all been found to occur with aging, and recent microarray analyses in rodent models have linked these processes and others to age-related memory impairment. However, whether these brain changes are also associated with metabolic variables is not known. Aging monkeys exhibit several metabolic changes similar to those seen in humans. Here, we tested peripheral-brain relationships in six young (7.0 +/- 0.3 years) and six aged (23.5 +/- 0.7 years) female rhesus monkeys. Animal cognition was gauged with a variable delay task; blood constituents were assessed with a serum chemistry panel emphasizing markers of metabolic dysfunction; mitochondrial function was measured from the hippocampus of one hemisphere; and the CA1 and dentate gyrus regions of the other hippocampus were dissected out for gene expression microarray analysis. Aged animals showed reduced performance on the behavioral task, exhibited aspects of metabolic dysregulation including increased insulin, triglyceride, and chylomicron levels (consolidated into a peripheral metabolic index), and showed a significant age-related reduction in State III oxidation, a measure of mitochondrial function. Microarray analyses revealed hundreds of genes that correlated with the peripheral metabolic index. However, DAVID statistical pathway analyses showed that upregulated inflammatory genes in CA1 and downregulated transcriptional regulation genes in dentate gyrus and CA1 were particularly overrepresented among genes correlated with the peripheral index. Thus, the association of metabolic variables with specific neuropathological processes in different regions of the hippocampal formation may have implications for mechanisms through which peripheral metabolism alters the risk for Alzheimers disease.
Publication Title
Aging-related gene expression in hippocampus proper compared with dentate gyrus is selectively associated with metabolic syndrome variables in rhesus monkeys.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, this protein is specifically expressed by memory B cells (MBCs) and is preferentially localized in subephitelial regions of lymphoid tissues. An expansion of FCRL4+ B cells has been shown in blood or other tissues in various infectious or autoimmune pathologies. In the present work, we generated and characterized in vitro FCRL4+ B cells from purified MBCs using T-dependent and/or T-independent stimulation. FCRL4+ B cells account for 17% of cells generated at day-4 of culture. Transcriptomic and phenotypic analysis of FCRL4+ cells show that they are closely related to FCRL4+ tonsillar MBCs. Interestingly, these cells highly express inhibitory receptors genes as described for exhausted FCRL4+ MBCs in the blood of HIV-viremic individuals. In agreement, in vitro generated FCRL4+ B cells show a significant underexpression of cell cycle genes with a two fold weaker number of cell division compared to FCRL4- cells. Finally, resulting from their reduced proliferation and differentiation potential, we show that FCRL4+ cells are not prone to generate plasma cells, contrary to FCRL4- cells. Given the difficulty to access to in vivo FCRL4+ cells, our in vitro model could be of major interest to study the biology of normal and pathological FCRL4+ cells.
Publication Title
Characterization of human FCRL4-positive B cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent genetic studies in mice have established a key role for the nuclear receptor coregulator Trim24 in liver tumor suppression and provided evidence that Trim24 suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (Rara)-dependent transcription and cell proliferation. However, it is unknown which downstream targets of Rara regulated by Trim24 are critical for tumorigenesis. We report here that loss of Trim24 results in the overexpression of interferon (IFN)/STAT pathway genes in the liver, a process that occurs early in tumorigenesis and is more pronounced in tumors, despite the enhanced expression, late in the disease, of negative regulators such as Usp18, Socs1 and Socs2.
Publication Title
Tripartite motif 24 (Trim24/Tif1α) tumor suppressor protein is a novel negative regulator of interferon (IFN)/signal transducers and activators of transcription (STAT) signaling pathway acting through retinoic acid receptor α (Rarα) inhibition.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 20 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Gene expression in response to changes in sulfur supply was studied in P. aeruginosa E601, a cystic fibrosis isolate that displays mucin sulfatase activity, and in P. aeruginosa PAO1. A large family of genes was found to be upregulated by sulfate limitation in both isolates, encoding sulfatases and sulfonatases, transport systems, oxidative stress proteins, and a sulfate-regulated TonB/ExbBD complex. These genes were localized in five distinct islands on the genome, and encoded proteins with a significantly reduced content of cysteine and methionine. Growth of P. aeruginosa E601 with mucin as sulfur source led to a sulfate starvation response, but also to induction of genes involved with type III secretion systems.
Publication Title
Transcriptomic analysis of the sulfate starvation response of Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE43144- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
One of the key questions in developmental biology is how from universally shared molecular mechanisms and pathways, is it possible to generate organs displaying similar or complementary functions, with a wide range of different shapes or tissue organization? The dentition represents a valuable system to address the issues of differential molecular signatures generating specific tooth types. We performed a comparative transcriptomic analysis of developing murine lower incisors, mandibular molars and maxillary molars at the developmental cap stage (E14.5) prior to recognizable tooth shape and cusp pattern.
Publication Title
Molars and incisors: show your microarray IDs.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Background: Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruptions well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleeps relationship to cognitive aging.
Publication Title
Deep sleep and parietal cortex gene expression changes are related to cognitive deficits with age.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Rattus norvegicus
- 49 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Recent microarray studies in the hippocampus of rodents or Alzheimers disease (AD) subjects have identified a substantial number of cellular pathways/processes correlated with aging and cognitive decline. However, the temporal relationships among these expression changes or with cognitive impairment have not been studied in depth. Here, using Affymetrix microarrays, immunohistochemistry and Morris water maze cognitive testing across 5 age groups of male F344 rats (n=9-15/group, one microarray per animal), we systematically analyzed the temporal sequence and cellular localization of aging changes in expression. These were correlated with performance scores on the hippocampus-dependent Morris Water Maze task. Significant microarray results were sorted in to Early, Intermediate, Midlife, and Late patterns of expression, and functionally categorized (Early- downregulated neural development, lipid synthesis and energy-utilization; upregulated ribosomal synthesis, growth, stress/inflammatory, lysosome and protein/lipid degradation. Intermediate- increased defense/inflammatory activation and decreased transporter activity; Midlife- downregulated energy-dependent signaling and neurite growth, upregulated astroglial activation, Ca2+-binding, cholesterol/lipid trafficking, myelinogenic processes and additional lysosome/inflammation; Late- further recruitment of genes in already-altered pathways). Immunohistochemistry revealed a primarily astrocytic localization of the processes upregulated in midlife, as well as increased density of myelin proteins. Evidence of cognitive impairment first appeared in the 12-month-old group (midlife) and was increased further in the 23-month-old group, exhibiting the highest correlations with some upregulated genes related to cholesterol transport (e.g., Apoe, Abca2), protein management and ion binding. Some upregulated genes for inflammation (Il6st) and myelinogenesis (Pmp22) also correlated with impairment. Together, the data are consistent with a novel sequential cascade model of brain aging in which metabolic alterations early in maturity are followed by inflammation and midlife activation of an astrocyte-centered cholesterol trafficking pathway that stimulates oligodendrocyte remyelination programs. Importantly, this cholesterol trafficking pathway also may compete for astroglial bioenergetic support of neurons, in turn, leading to downregulation of energy-dependent pathways needed to sustain cognitive functions.
Publication Title
Hippocampal and cognitive aging across the lifespan: a bioenergetic shift precedes and increased cholesterol trafficking parallels memory impairment.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 23 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of ryanodine receptor Ca2+ release, reverses aging-induced memory impairment and neuronal Ca2+ dysregulation. Here, we test the hypothesis that FKBP1b also can protect downstream transcriptional networks from aging-induced dysregulation. We gave hippocampal microinjections of FKBP1b-expressing viral vector to male rats at either 13-months-of-age (long-term) or 19-months-of-age (short-term) and tested memory performance in the Morris water maze at 21-months-of-age. Aged rats treated short- or long-term with FKBP1b substantially outperformed age-matched vector controls and performed similarly to each other and young controls. Transcriptional profiling in the same animals identified 2342 genes whose hippocampal expression was up-/down-regulated in aged controls vs. young controls (the aging effect). Of these aging-dependent genes, 876 (37%) also showed altered expression in aged FKBP1b-treated rats compared to aged controls, with FKBP1b restoring expression of essentially all such genes (872/876, 99.5%) in the direction opposite the aging effect and closer to levels in young controls. This inverse relationship between the aging and FKBP1b effects suggests that the aging effects arise from FKBP1b deficiency. Functional category analysis revealed that genes downregulated with aging and restored by FKBP1b associated predominantly with diverse brain structure categories, including cytoskeleton, membrane channels and extracellular region. Conversely, genes upregulated with aging but not restored by FKBP1b associated primarily with glial-neuroinflammatory, ribosomal and lysosomal categories. Immunohistochemistry confirmed aging-induced rarefaction, and FKBP1b-mediated restoration, of neuronal microtubular structure. Thus, a previously-unrecognized genomic network modulating diverse brain structural processes is dysregulated by aging and restored by FKBP1b overexpression.
Publication Title
FK506-Binding Protein 12.6/1b, a Negative Regulator of [Ca<sup>2+</sup>], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Retinoic acid (RA), an active derivative of the liposoluble vitamin A (retinol), acts as an important signaling molecule during embryonic development, regulating phenomenons as diverse as anterior-posterior axial patterning, forebrain and optic vesicle development, specification of hindbrain rhombomeres, pharyngeal arches and second heart field, somitogenesis, and differentiation of spinal cord neurons. This small molecule directly triggers gene activation by binding to nuclear receptors (RARs), switching them from potential repressors to transcriptional activators. The repertoire of RA-regulated genes in embryonic tissues is poorly characterized. We performed a comparative analysis of the transcriptomes of murine wild-type and Retinaldehyde Dehydrogenase 2 null-mutant (Raldh2-/-) embryos - unable to synthesize RA from maternally-derived retinol - using Affymetrix DNA microarrays. Transcriptomic changes were analyzed in two embryonic regions: anterior tissues including forebrain and optic vesicle, and posterior (trunk) tissues, at early stages preceding the appearance of overt phenotypic abnormalities. Several genes expected to be downregulated under RA deficiency appeared in the transcriptome data (e.g. Emx2, Foxg1 anteriorly, Cdx1, Hoxa1, Rarb posteriorly), whereas reverse-transcriptase-PCR and in situ hybridization performed for additional selected genes validated the changes identified through microarray analysis. Altogether, the affected genes belonged to numerous molecular pathways and cellular/organismal functions, demonstrating the pleiotropic nature of RA-dependent events. In both tissue samples, genes upregulated were more numerous than those downregulated, probably due to feedback regulatory loops. Bioinformatic clustering analysis allowed us to extract groups of genes displaying similar behaviors in mutant tissue samples. These data give an overview of the gene expression changes occurring under a state of embryonic RA deficiency, and provide new candidate genes and pathways for a better understanding of retinoid-dependent molecular events.
Publication Title
Transcriptomic analysis of murine embryos lacking endogenous retinoic acid signaling.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Gene expression profiling in dopaminergic brain structures of rats self-administering cocaine. Effect of histone deacetylase inhibition
Publication Title
Inhibition of histone deacetylases in rats self-administering cocaine regulates lissencephaly gene-1 and reelin gene expression, as revealed by microarray technique.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples