Gene transfer vectors based on gamma-retroviruses target actively transcribing genes indicating that the cellular gene expression profile can be predictive of their integration pattern. Therefore, different culture conditions leading to different transcriptional activity may translate into differences in the profile of targeted genes in cells transduced with these vectors. Recent data from two gene therapy trials for SCID-X1 conducted in France and the UK suggested that small differences between in vitro stimulation conditions could explain the disparity in the frequency of common integrations sites observed in the two studies.
No associated publication
Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis.
Specimen part, Cell line
View SamplesThese datasets describe a melanocyte specific, HIF1A-Dependent / Hypoxia-Responsive gene expression signature defined by the regulation of genes critical to metabolism, chromatin and transcriptional regulation, vascularization and cellular invasivness. These genes provide lineage specific targets for refinement of diagnostic markers associated with primary melanoma tumor metastatic potential, and also provides novel molecular targets for therapeutic strategies targeting metastatic disease progression.
Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis.
Specimen part, Cell line
View SamplesWe hypothesize that germline variation influences susceptibility to aggressive prostate tumor
GNL3 and SKA3 are novel prostate cancer metastasis susceptibility genes.
Specimen part
View SamplesRRP1B is a breast cancer metastasis suppressor that interacts with various regulators of gene transcription
Metastasis-associated protein ribosomal RNA processing 1 homolog B (RRP1B) modulates metastasis through regulation of histone methylation.
Specimen part, Cell line
View SamplesNdn is a candidate metastasis suppressor gene that has been reported to regulate transcription.
Necdin is a breast cancer metastasis suppressor that regulates the transcription of c-Myc.
Cell line
View SamplesAAV gene therapy has recently been approved for clinical use and shown to be efficacious and safe in a growing number of clinical trials. However, the safety of AAV as a gene therapy has been challenged by a few studies that documented hepatocellular carcinoma (HCC) after AAV gene delivery in mice. The association between AAV and HCC has been difficult to reconcile and is the subject of intense debate because numerous AAV studies have not reported toxicity. Here, we report a comprehensive study of HCC in a large number of mice following therapeutic AAV gene delivery. Using a sensitive high-throughput integration site-capture technique and global expressional analysis, we found that AAV integration into the Rian locus and the over-expression of a proximal gene, Rtl1, were associated with HCC. In addition, we identify a number of genes with differential expression that maybe useful in the study, diagnosis and treatment of HCC. We demonstrate that AAV vector dose, enhancer-promoter selection, and the timing of gene delivery are the defining factors in AAV-mediated insertional mutagenesis. Our results help explain the AAV-mediated genotoxicity previously observed and have important implications for the design of both safer AAV vectors and gene therapy studies.
No associated publication
Sex, Specimen part, Disease
View SamplesIn two disparate models, we show that rapid revaccination following sublethal gamma radiation exposure rescues memory CD8+ T cell Responses.
Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.
No sample metadata fields
View SamplesAn animals ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brains immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglial RNAs were isolated and analyzed by global gene expression microarrays. Microglia transcriptome from CSD-S mice was enriched for pathways that describe phases of CNS healing to sterile injury including, inflammation, oxidative stress, debris clearance, and wound resolution. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or HC mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by leakage of blood-born substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.
Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility.
Specimen part
View SamplesThe resident skin microbiota plays a fundamental role in the control of skin physiology and growing evidence support the idea that, at this barrier site, both immunity and inflammatory processes are controlled by skin resident microbiota. However, how defined skin microbes influence the skin immune system under both steady state conditions and inflammatory settings remains poorly understood. Obesity has been linked to increased prevalence of skin inflammatory disorders.
No associated publication
Specimen part
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