Public transcriptomics studies have shown that several genes display pronounced gender differences in their expression in the human brain, and these differences may influence the clinical manifestations and risk for neuronal disorders. While disease relevant implications have already been proposed for gender differences in hormone levels, life style and genetic diversity, a systems level analysis of brain gene expression disparities between the genders in the context of brain disorders like Alzheimers disease (AD) has not yet been conducted.
Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau Expression and Phosphorylation: Possible Implications for Tauopathies.
Specimen part, Treatment
View SamplesExpression data from NIH-3T3 cells treated with mock, 100 U/ml IFN alpha or 100 U/ml gamma for 1 or 3h on nt-RNA labeled for 30-60 min at different times of interferon treatment
High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay.
No sample metadata fields
View SamplesDifferential gene expression caused by 1h and 3h of IFN alpha or gamma treatment was analyzed in total cellular RNA of NIH-3T3 cells compared to mock
High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay.
No sample metadata fields
View SamplesMicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection. Sequencing of small RNAs from serum confirmed the presence of miRNAs and revealed 11 parasite-derived miRNAs that were detectable by 8 weeks post S.mansoni infection. Overall design: Small RNA content in serum of naïve and Schistosoma mansoni infected mice were examined in two different librarys. 1- prepared according to the 290 Illumina small RNA Sample Preparation Kit version 1.5 and sequenced on the GAIIX and 2- prepared according to the TruSeq Small RNA protocol (without size-selecting small 295 RNA) and sequenced on the HiSeq2
Parasite-derived microRNAs in host serum as novel biomarkers of helminth infection.
Sex, Cell line, Subject
View SamplesUterine NK cells (uNK) play a role in the regulation of placentation but their functions in non-pregnant endometrium are not understood. We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil, a progesterone receptor modulator (PRM). We now compare global endometrial gene expression in asoprisnil-treated versus control women and demonstrate a statistically significant reduction of genes in the IL-15 pathway, known to play a key role in uNK development and function. Suppression of IL-15 by asoprisnil was also observed at mRNA level (p<0.05), and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium (p<0.001). IL-15 levels in normal endometrium are progesterone-responsive. Progesterone receptor (PR) positive stromal cells transcribe both IL-15 and IL-15RA. Thus, the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK, supporting their expansion and differentiation. In asoprisnil-treated endometrium, there is a marked down-regulation of stromal PR expression and virtual absence of uNK. These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay between endometrial stromal cells, uNK and spiral arteries affecting physiological and pathological endometrial bleeding.
Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil.
Sex, Specimen part
View SamplesWe aimed to identify the gene network and pathway biology associated with response to vaccine administration by determining genome-wide alterations in host RNA in children
Sex-Differential Non-Vaccine-Specific Immunological Effects of Diphtheria-Tetanus-Pertussis and Measles Vaccination.
Sex, Age, Specimen part
View SamplesWe aimed to identify the gene network and pathway biology associated with neonatal sepsis by determining genome-wide alterations in host RNA in infected infants
Identification of a human neonatal immune-metabolic network associated with bacterial infection.
Sex, Specimen part
View SamplesGenetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many of the potential applications are still limited by the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. These challenges could be overcome by the use of adult tissue stem cells derived from hPSCs, as their restricted potential could limit the differentiation towards other undesired linages, and allow in vitro expansion and long- term propagation of fully differentiated tissue. To isolate adult stem cells from hPSCs, we applied genome-editing to generate an LGR5-GFP reporter system and subsequently developed a differentiation protocol for human intestinal tissue comprising an adult stem cell niche and all major cell types of the adult intestine. This novel derivation protocol is highly robust and even permits the isolation of intestinal organoids without the LGR5 reporter. Transcriptional profiling, electron microscopy and functional analysis revealed that such human organoid cultures could be derived with high purity, and a composition and morphology similar to that of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. With our ability to genetically engineer hPSCs using site-specific nucleases, this adult stem cell system provides a novel platform by which to study human intestinal disease in vitro. Overall design: RNA from primary organoid samples was isolated from organoid lines that were both cultured for 1-6 months and derived from duodenum, ileum, or rectum biopsies of human subjects as described previously (Sato et al., Gastroenterology 2011) grown in media called WENR+inhibitors. RNA was also isolated from various steps in the culturing and differentiation protocol.
Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells.
No sample metadata fields
View SamplesAn experiment was performed to analyze the effect of knockdown of dpf3 during zebrafish embryogenesis.Morpholino against dpf3 and control morpholino were injected into eggs and eggs were kept under standard conditions for 72 hours. Embroys were harvested, total RNA was extracted and used for microarray analysis.
Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex.
Time
View SamplesBreast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis-free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2r-/- mice), we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases.
Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape.
Specimen part
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