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Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by increased ovarian androgen production, arrested follicle development, and is frequently associated with insulin resistance. These PCOS phenotypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss. To examine whether the perturbations in follicle growth and the intrafollicular environment affects development of the mature PCOS oocyte, genes that are differentially expressed in PCOS compared to normal oocytes were defined using microarray analysis. This analysis detected approximately 8000 transcripts. Hierarchical clustering and principal component analysis revealed differences in global gene expression profiles between normal and PCOS oocytes. 374 genes had a statistically-significant increase or decrease in mRNA abundance in PCOS oocytes. A subset of these genes was associated with chromosome alignment and segregation during mitosis and/or meiosis, suggesting that increased mRNAs for these proteins may negatively affect oocyte maturation and/or early embryonic development. Of the 374 differentially expressed genes, 68 contained putative androgen receptor, retinoic acid receptor, and/or peroxisome proliferating receptor gamma binding sites, including 9 of the genes involved in chromosome alignment and segregation. These analyses demonstrated that normal and PCOS oocytes that are morphologically indistinguishable and of high quality exhibit different gene expression profiles. Furthermore, altered mRNA levels in the PCOS oocyte may contribute to defects in meiosis and/or mitosis which might impair oocyte competence for early development and therefore contribute to poor pregnancy outcome in PCOS.
Publication Title
Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis.
Sample Metadata Fields
No sample metadata fields
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GSE1615- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects 5-10% of reproductive aged women. The hallmark characteristic of PCOS is increased ovarian androgen synthesis. Previous studies by our laboratory demonstrated that increased androgen synthesis is a stable biochemical phenotype of PCOS theca cells which are the primary source of ovarian androgen production. The increase in theca cell steroidogenesis was due to an increase in expression of several steroidogenic enzymes including CYP17 and CYP11A but not StAR. Interestingly, the anti-epileptic drug valproic acid induces increased theca cell androgen synthesis and increased CYP17 and CYP11A mRNA levels. In this study we have characterized the gene expression profiles of theca cells obtained from normal or polycystic ovaries which were maintained in the absence (UNT) or presence (VPA) of valproic acid. The data identifed new candidate genes and novel signaling pathways which may contribute to the manifestation of PCOS phenotypes including increased androgen production. The experiments in this study were carried using the Affymetrix U133A and U133B oligonucleotide chips.
Publication Title
Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 47 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina humanRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 45 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dysregulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation, gene expression mediated by the transcription factor NF-B is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-B up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dysregulated basal NF-B activity may contribute to the mild pro-inflammatory state of aging.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina humanRef-8 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dysregulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation, gene expression mediated by the transcription factor NF-B is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-B up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dysregulated basal NF-B activity may contribute to the mild pro-inflammatory state of aging.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina humanRef-8 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dysregulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation, gene expression mediated by the transcription factor NF-B is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-B up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dysregulated basal NF-B activity may contribute to the mild pro-inflammatory state of aging.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 268 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The transcriptional responses of human hosts towards influenza viral pathogens are important for understanding virus-mediated immunopathology. Despite great advances gained through studies using model organisms, the complete temporal host transcriptional responses in a natural human system are poorly understood. In a human challenge study using live influenza (H3N2/Wisconsin) viruses, we conducted a clinically uninformed (unsupervised) factor analysis on gene expression profiles and established an ab initio molecular signature that strongly correlates to symptomatic clinical disease. This is followed by the identification of 42 biomarkers whose expression patterns best differentiate early from late phases of infection. In parallel, a clinically informed (supervised) analysis revealed over-stimulation of multiple viral sensing pathways in symptomatic hosts and linked their temporal trajectory with development of diverse clinical signs and symptoms. The resultant inflammatory cytokine profiles were shown to contribute to the pathogenesis because their significant increase preceded disease manifestation by 36 hours. In subclinical asymptomatic hosts, we discovered strong transcriptional regulation of genes involved in inflammasome activation, genes encoding virus interacting proteins, and evidence of active anti-oxidant and cell-mediated innate immune response. Taken together, our findings offer insights into influenza virus-induced pathogenesis and provide a valuable tool for disease monitoring and management in natural environments.
Publication Title
Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functionally. Here, we sought to identify lncRNAs differentially expressed during replicative senescence. We compared lncRNAs expressed in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those expressed in senescent, late-passage, 'old' fibroblasts (PDL 52) by RNA sequencing (RNA-Seq). Numerous transcripts in all lncRNA groups (antisense lncRNAs, pseudogene-encoded lncRNAs, previously described lncRNAs and novel lncRNAs) were validated using reverse transcription (RT) and real-time, quantitative (q)PCR. Among the novel senescence-associated lncRNAs (SAL-RNAs) showing lower abundance in senescent cells, SAL-RNA1 (XLOC_023166) was found to delay senescence, because reducing SAL-RNA1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive ß-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel lncRNAs changes with senescence and suggests that SAL-RNAs play direct regulatory roles in this important cellular process. Overall design: RNA was extracted from both young and senescent WI-38 cells and used for total RNA-Seq.
Publication Title
Senescence-associated lncRNAs: senescence-associated long noncoding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
microRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific mRNAs. Altered expression of circulating miRNAs have been associated with age-related diseases including cancer and cardiovascular disease. Although we and others have found an age-dependent decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs), little is known about the role of circulating miRNAs in human aging. Here, we examined miRNA expression in human serum from young (mean age 30 years) and old (mean age 64 years) individuals using next generation sequencing technology and real-time quantitative PCR. Of the miRNAs that we found to be present in serum, three were significantly decreased in 20 older individuals compared to 20 younger individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in humans, these miRNAs are also present at lower levels in the serum of elderly rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs involved in inflammatory pathways and miR-181a was found to correlate negatively with the pro-inflammatory cytokines IL-6 and TNFa and to correlate positively with the anti-inflammatory cytokines TGFb and IL-10. These results suggest that circulating miRNAs may be a biological marker of aging and could also be important for regulating longevity. Identification of stable miRNA biomarkers in serum could have great potential as a noninvasive diagnostic tool as well as enhance our understanding of physiological changes that occur with age. Overall design: Examination of microRNAs isolated from human serum from 11 young (mean age 30 yrs) and 11 old (mean age 64 yrs) individuals and from peripheral blood mononuclear cells from one young (30 yr) and one old (64 yr) individual.
Publication Title
Age-related changes in microRNA levels in serum.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Emerging evidence suggests the potential involvement of altered regulation of miRNA in the pathogenesis of cancers, and these genes are thought to function as both tumor suppressors and oncogenes. Using microRNA microarrays, we identify several miRNAs aberrantly expressed in human ovarian cancer tissues and cell lines. miR-221 stands out as a highly elevated miRNA in ovarian cancer, while miR-21 and several members of the let-7 family are found downregulated. Public databases were used to reveal potential targets for the highly differentially expressed miRNAs. In order to experimentally identify transcripts whose stability may be affected by the differentially expressed miRNAs, we transfected precursor miRNAs into human cancer cell lines and used oligonucleotide microarrays to examine changes in the mRNA levels.
Publication Title
MicroRNA expression and identification of putative miRNA targets in ovarian cancer.
Sample Metadata Fields
Sex
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