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GSE59786
Homo sapiens
39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray used to detail the global gene transcription underlying sorted IFNg+ and IFNg- Tregs (CD4+CD25+CD127lo) and Tconv (CD4+CD25-CD127+) for fresh (unexpanded) and 14 day expanded cells from human blood.
Publication Title
Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226.
Sample Metadata Fields
Specimen part, Disease stage, Treatment, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify the molecular characterisitics of parallel lineage-biased MPP populations arising from hematopoietic stem cells (HSC) we conducted genome-wide analyses of hematopoietic stem, progenitor and mature myeloid cell populations using Affymetrix Gene ST1.0 arrays.
Publication Title
Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 166 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Polyoma virus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. Microscopic descriptions of PVAN are very similar to T-cell mediated rejection (TCMR) and have unclear underlying molecular mechanisms. To identify PVAN-specific gene expression, we analyzed 162 kidney biopsies with and without PVAN for global gene expression. Unsupervised hierarchical clustering analysis of all 162 biopsies revealed high similarity between PVAN and TCMR gene expression. Increasing the stringency for the specificity (p <0.001 and >2-fold expression) between PVAN and TCMR, 158 and 252 unique PVAN and TCMR injury-specific probesets were observed, respectively. While TCMR-specific probeset were overwhelmingly involved in immune response costimulation (CTLA4, CD28, CD86) and TCR (NFATC2, LCP2) signaling, PVAN-specific probesets were mainly related to viral replication process (IFITM1, LTF, NOSIP, RARRES3), RNA polymerase assembly (POLR2l, TAF10, RPS15) and pathogen recognition receptors (C1QA, C3, CFD). A principal component analysis using these genes further confirmed the most optimal separation between the 3 different clinical phenotypes. Validation of 4 PVAN-specific probesets (RPS15, CFD, LTF, and NOSIP) by QPCR and further confirmation by IHC of 2 PVAN-specific proteins with anti-viral function (LTF and IFITM1) was done, showing significantly higher expression within interstitial cellular infiltrates and in tubuli in PVAN specimens as compared to TCMR and NL kidney biopsies. In conclusion, even though PVAN and TCMR kidney allografts share great similarities on gene perturbation, particular PVAN-specific transcripts were identified with well-known anti-viral properties that provide tools for discerning PVAN and AR as well as attractive targets for rational drug design.
Publication Title
Intragraft Antiviral-Specific Gene Expression as a Distinctive Transcriptional Signature for Studies in Polyomavirus-Associated Nephropathy.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 138 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Endometriosis, an estrogen-dependent, progesterone-resistant, inflammatory disorder affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Since the uterine lining (endometrium) in women with endometriosis has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n=148 archived endometrial samples from women with endometriosis or without endometriosis (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with endometriosis or no endometriosis involved two binary decisions each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no endometriosis from endometriosis, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified endometriosis with 90-100% accuracy, were cycle phase-specific or independent, and utilized relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism and growth factor signaling in endometrium of women with endometriosis. Similar findings were observed with other disorders versus controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic endometriosis with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate-genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular differences in the presence of endometriosis and other uterine/pelvic pathologies raises the broader biological question of their impact on the steroid hormone response and normal functions of this tissue.
Publication Title
Molecular classification of endometriosis and disease stage using high-dimensional genomic data.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Clinically isolated syndrome (CIS) refers to the earliest clinical manifestation of multiple sclerosis (MS). Currently there are no prognostic biological markers that accurately predict conversion of CIS to clinically definite MS (CDMS). Furthermore, the earliest molecular events in MS are still unknown. We used microarrays to study gene expression in nave CD4+ T cells from 37 CIS patients at time of diagnosis and after one year. Supervised machine-learning methods were used to build predictive models of disease conversion. We identified 975 genes whose expression segregated CIS patients into 4 distinct subgroups. A subset of 108 genes further discriminated patients from one of these (group#1) from other CIS patients. Remarkably, 92% of patients from group #1 converted to CDMS within 9 months. Consistent downregulation of TOB1, a critical regulator of cell proliferation, was characteristic of group #1 patients. Decreased TOB1 expression at the RNA and protein levels was also confirmed in experimental autoimmune encephalomyelitis (EAE). Finally, a genetic association was observed between TOB1 variation and MS progression in an independent cohort. These results indicate that CIS patients at high risk of conversion have impaired regulation of T cell quiescence resulting in earlier activation of pathogenic CD4+ cells.
Publication Title
Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 105 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Airway epithelial brushings were obtained for microarray analysis by research bronchoscopy in 62 subjects with mild-to-moderate asthma not on inhaled steroids and 43 healthy controls. Asthma subjects were stratified into 2 subgroups, Th2 high and Th2 low asthma, based on their expression of a three-gene signature of Type 2 inflammation: POSTN, SERPINB2, and CLCA1.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 84 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Epidemiological studies indicate that progestin-containing contraceptives may increase susceptibility to HIV and other infections; however, underlying mechanisms involving the upper female reproductive tract are undefined. To determine the effects of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) on gene expression and physiology of the human endometrial and cervical transformation zone (TZ), microarray analyses were performed on whole tissue biopsies. In endometrium, activated pathways included leukocyte chemotaxis, attachment, and inflammation in DMPA (z>2.5) and LNG-IUS (z>3.5) users, and regulation of pattern recognition receptors and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability genes, but not those of immune functions. Together, these results indicate that progestins influence expression of immune-related genes in endometrium that would be expected to result in the local recruitment of HIV target cells, and thus may increase HIV susceptibility. It is important to consider the upper reproductive tract in the assessment of effects of contraceptives that may influence susceptibility to pathogens, such as HIV.
Publication Title
Progestin-Containing Contraceptives Alter Expression of Host Defense-Related Genes of the Endometrium and Cervix.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P4, we compared early (6-h), intermediate (48-h), and late (14-day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESFs) from women with endometriosis (hESFendo) to hESFs from women without endometriosis (hESFnonendo). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESFs were isolated and treated with P4 (1 M) plus estradiol (E2) (10 nM), E2 alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P4 in both hESFnonendo and hESFendo, although a blunted response to P4 was observed in the latter. The normal response of hESF to P4 involves a tightly regulated kinetic cascade involving key components in the P4 receptor and MAPK signaling pathways that results in inhibition of E2-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESFendo early response to P4. The abnormal response of this cell type to P4 may contribute to compromised embryonic implantation and infertility in women with endometriosis.
Publication Title
Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Intravaginal HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract (FRT) might contribute to the lower-than-expected efficacy of HIV microbicides. In this observational crossover study, 28 healthy female volunteers used no product (control cycle) or used a nightly application of intravaginal nonoxynol-9 gel [N9] as a 'failed' microbicide or the universal placebo gel [UPG] as a 'safe' gel, from the end of menses to the mid-luteal phase (intervention cycles). They then underwent sample collection for measurements of T-cell phenotypes, transcriptional profiling, and protein levels from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI) intervention:control fold-changes in relevant phenotype levels. Exposure to N9 and UPG generated a common 'harm signature' that included transcriptional up-regulation of inflammatory genes CCL20 and IL8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor and increased percentages of terminally differentiated CD4+ effector T-cells in the endocervix, and transcriptional up-regulation of inflammatory mediators KIR3DS1, glycodelin-A, and osteopontin in the endometrium. These results underscore the need to consider the effects of microbicide agents and gel excipients on the upper FRT in studies of vaginal microbicides. Given the pro-inflammatory effects of UPG on the upper FRT, it may not be a suitable placebo for microbicide trials.
Publication Title
Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9) on the Upper Female Reproductive Tract: A Randomized Crossover Study.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This series represents isolated alveolar macrophages from human subjects.
Publication Title
A distinctive alveolar macrophage activation state induced by cigarette smoking.
Sample Metadata Fields
No sample metadata fields
View Samples