We examine how NGS sequencing of sperm can provide a window as to how particular perturbations of the sperm RNA profile from baseline may be indicative of male factor infertility, and may thus provide direction as to proper course of infertility treatment for couple. Overall design: NGS RNA-seq of 72 sperm samples from male partner of couples undergoing fertility treatment
Absence of sperm RNA elements correlates with idiopathic male infertility.
No sample metadata fields
View SamplesContext: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive- aged women, is associated with systemic low-grade inflammation. Objective: We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients. Design: Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines. Setting: This was a university-based study. Patients: Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files. Interventions:GCcytokine/chemokinemRNAswere identified and analyzed by gene-chip microarrays/ qPCR before and after culture withhumanchorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed. Main Outcome Measures: Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index. Results: The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production. Conclusions: Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype.
Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome.
Specimen part
View SamplesCD70TG mice are a model for sterile chronic immune activation and develop Anemia of Inflammation, which is dependent on the production of Ifng by effector CD4 and CD8 T cells.
Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis.
Specimen part
View SamplesAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (p103) and 411 aberrantly spliced genes (p105). The aberrantly spliced genes were highly enriched in cell adhesion (p1057), especially cell-matrix as opposed to cell-cell adhesion. Most of the enriching genes encode transmembrane or secreted as opposed to nuclear or cytoplasmic proteins. The differentially expressed genes were not biologically enriched. In the anterior horn enriched mRNA pool, we could not clearly identify mRNA signals or biological enrichment. These findings, perturbed and up-regulated cell-matrix adhesion, suggest possible mechanisms for the contiguously progressive nature of motor neuron degeneration.
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.
Sex, Age, Specimen part
View SamplesMolecular heterogeneity among spiral ganglion neurons (SGNs) in the mouse cochlea was investigated in two genetic backgrounds: 1) wildtype, 2) Vglut3-/-, which lack inner hair cell-driven glutamatergic activation of SGNs. Overall design: Individual spiral-ganglion neurons expressing the fluorescent reporter tdTomato were dissociated and manually placed into PCR tubes; single-cell libraries were made by the Smart-seq2 approach; sequencing was done using the NextSeq platform (Illumina) at an average read depth of 4.5 million; bioinformatic analysis was conducted in R. Genotypes: bhlhb5::cre/+; Ai14/+ (wildtype) and bhlhb5::cre/+;Ai14/+; Vglut3-/- (Vglut3-/-). Age: P25-P27
Sensory Neuron Diversity in the Inner Ear Is Shaped by Activity.
Subject
View SamplesNormal adult liver is uniquely capable of renewal
Restoration of liver mass after injury requires proliferative and not embryonic transcriptional patterns.
Age
View SamplesNrf2 is an important therapeutic target as activation of this pathway detoxifies harmful insults and reduces oxidative stress. However, the role of Nrf2 in cancer biology is controversial. Protection against oxidative stress and inflammation can confer a survival advantage to tumor cells, leading to a poor prognosis, and constitutive activation of Nrf2 has been detected in numerous tumors. In our study, we examined the role of two clinically relevant classes of Nrf2 activators, the synthetic triterpenoids (CDDO-Im and CDDO-Me) and dimethyl fumarate (DMF) in lung cancer.
Dimethyl fumarate and the oleanane triterpenoids, CDDO-imidazolide and CDDO-methyl ester, both activate the Nrf2 pathway but have opposite effects in the A/J model of lung carcinogenesis.
Sex, Specimen part
View SamplesWhile early stages of clear cell renal cell carcinoma (ccRCC) are curable, survival outcome for metastatic ccRCC remains poor. The purpose of the current study was to apply a new individualized bioinformatics analysis (IBA) strategy to these transcriptome data in conjunction with Gene Set Enrichment Analysis of the Connectivity Map (C-MAP) database to identify and reposition FDA-approved drugs for anti-cancer therapy. We demonstrated that one of the drugs predicted to revert the RCC gene signature towards normal kidney, pentamidine, is effective against RCC cells in culture and in a RCC xenograft model. Most importantly, pentamidine slows tumor growth in the 786-O human ccRCC xenograft mouse model. To determine which genes are regulated by pentamidine in a human RCC cell line, 786-O, we treated these cells with pentamidine and performed transcriptional profiling analysis.
Computational repositioning and preclinical validation of pentamidine for renal cell cancer.
Cell line, Treatment
View SamplesProper cortical development relies on the balance of neuronal migration and proliferation. We investigated the gene expression differences of mouse knock-outs for Lissencephaly in humans.
Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.
Specimen part
View SamplesPURPOSE:
Unique gene expression profile based on pathologic response in epithelial ovarian cancer.
No sample metadata fields
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