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GSE137765
Homo sapiens
97 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.
Publication Title
Differential Effects of the Hormonal and Copper Intrauterine Device on the Endometrial Transcriptome.
Sample Metadata Fields
Age, Specimen part
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
- 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
- 12 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human cytomegalovirus induces a pro-inflammatory monocyte following infection. To begin to address how HCMV induces these rapid changes in infected monocytes, we examined the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of pro-inflammatory genes were upregulated within 4 hours post infection.
Publication Title
Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 168 Downloadable Samples
Illumina HiSeq 2500
Description
Adult zebrafish are capable of regenerating cardiac tissue following ventricular resection within 30 days. We profiled both small RNA and mRNA expression in uninjured (0dpa), 1, 3, 7, 14, 21 and 30 days post amputation to study biological processes orchestrate each stage of regeneration. Overall design: Small and mRNA gene expression profiling during 0, 1, 3, 7, 14, 21 and 30 days post ventricular resection.
Publication Title
RegenDbase: a comparative database of noncoding RNA regulation of tissue regeneration circuits across multiple taxa.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The chronological lifespan (CLS) of Saccharomyces cerevisiae is defined as the number days that non-dividing cells remain viable, typically in stationary phase cultures or in water. CLS is extended by restricting glucose in the starting cultures, and is considered a form of caloric restriction (CR). Through a previous genetic screen our lab determined that deleting components of the de novo purine biosynthesis pathway also significantly increased CLS. Significant similarities in gene expression profiles between calorie restricted WT cells and a non-restricted ade4 mutant suggested the possibility of common gene expression biomarkers of all chronologically long lived cells that could also provide insights into general mechanisms of lifespan extension. We have identified additional growth conditions that extend CLS of WT cells, including supplementation of the media with isonicotinamide (INAM), a known sirtuin activator, or by supplementation with a concentrate collected from the expired media of a calorie restricted yeast culture, presumably due to an as yet unidentified longevity factor. Using these varied methods to extend CLS, we compared gene expression profiles in the aging cells (at day 8) to identify functionally relevant biomarkers of longevity. Nineteen genes were differentially regulated in all 4 of the long-lived populations relative to wild type. Of these 19 genes, viable haploid deletion mutants were available for 16 of them, and 12 were found to have a significant impact on CLS.
Publication Title
Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The development, homeostasis and function of B lymphocytes involve multiple rounds of B cell receptor (BCR)-controlled proliferation and prolonged maintenance. We analyzed the role of transcription factor Zfx, a recently identified regulator of stem cell maintenance, in B cell development and homeostasis. Conditional Zfx deletion in the bone marrow blocked B cell development at the pre-BCR selection checkpoint. Zfx deficiency in peripheral B cells caused impaired generation of the B-1 cell lineage, accelerated B cell turnover, depletion of mature recirculating cells, and delayed T-dependent antibody responses. Zfx-deficient B cells showed normal proximal BCR signaling, but impaired BCR-induced proliferation and survival. This was accompanied by aberrantly enhanced and prolonged integrated stress response, and delayed induction of Cyclin D2 and Bcl-xL proteins. Thus, Zfx restrains the stress response and couples antigen receptor signaling to B cell expansion and maintenance during development and peripheral homeostasis.
Publication Title
Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 282 Downloadable Samples
- Illumina HiSeq 2000
Description
Previous studies had shown that integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL "hotspots" associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provides a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation. Overall design: 282 samples, 3 biological replicates per strain
Publication Title
Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.
Sample Metadata Fields
Sex, Cell line, Subject
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HiSeq 2500
Description
We decribe the accessible chormatin landscape in RAS-induced (RIS) and NOTCH induced senescence (NIS) using ATAC-seq. By expressing active NOTCH (N1ICD) in the context of RIS, we find that N1ICD antagonises the formation of accessible regions in RIS. By performing co-cultures, we demonstrate that cells expressing a NOTCH1 ligand, JAGGED1, can antagonise the formation of RIS specific accessible regions. Overall design: mRNA profiles were IMR90 cells expressing ER:HRAS(G12V) and a control vector or MSCV miR30 shHMGA1 were generated. 6 biological replicates.
Publication Title
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 53 Downloadable Samples
- Illumina HiSeq 2500
Description
The meningeal space is occupied by a diverse repertoire of innate and adaptive immune cells. CNS injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation in CNS injury remains poorly understood. Here we describe group 2 innate lymphoid cells (ILC2s) as a novel cell type resident in the healthy meninges that is activated following CNS injury. ILC2s are present throughout the naïve mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile relative to lung ILC2s. After spinal cord injury, meningeal ILC2s are activated in an IL-33 dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild type lung-derived ILC2s into the meningeal space of IL-33R-/- animals improves recovery following spinal cord injury. These data characterize ILC2s as a novel meningeal cell type that responds to and functionally affects outcome after spinal cord injury, and could lead to new therapeutic insights for CNS injury or other neuroinflammatory conditions. Overall design: ILC2s were isolated from 10 week C57/Bl6 mice with and without spinal cord injury (1 day post injury). 5 mice were pooled per group, with meninges dissected, digested, and FACs sorted (CD45+/DAPI-/Lin–/St2+/Thy1+) directly into RNA lysis buffer.
Publication Title
Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples