We identified PHF5A as a functional synthetic-lethal hit in glioblastoma stem cells compared to normal neural stem cells. We wanted to perform analysis of RNA isoforms present in glioblastoma or normal neural stem cells with or without PHF5A depletion. We performed shRNA knockdown of PHF5A or used non-silencing shRNA as a control, selected infected cells with puromycin, and isolated RNA for sequencing. Overall design: We analyzed RNA from either normal neural stem cells or two different glioblastoma specimens aster either control knockdown, or two different shRNA sequences against the PHF5A gene transcript.
Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A.
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View SamplesHuman primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and derive embryonic stem cell properties.
Generation of pluripotent stem cells from adult human testis.
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View SamplesMycobacterium bovis (M. bovis) and Mycobacterium avium subspecies paratuberculosis (MAP) are important pathogens of cattle, causing bovine tuberculosis and Johne's disease respectively. M. bovis and MAP infect residential macrophages in the lung and intestines respectively and subvert the macrophage biology to create a survival niche. To investigate this interaction we simultaneously studied the transcriptional response of bovine monocyte-derived macrophages to infection with two strains of M. bovis (AF2122/97 and G18) and two strains of MAP (C & L1). Overall design: 120 samples were analysed in total; derived from six biological replicates (i.e. cells isolated from six cattle). Cells were left uninfected (medium only controls) or infected with either a M. bovis strain (AF2122/97 or G18) or a MAP strain (C or L1). Cells were harvested at 2, 6, 24 and 48h post infection.
Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom.
Subject, Time
View SamplesChronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction.
Behavioral and transcriptional patterns of protracted opioid self-administration in mice.
Specimen part
View SamplesJournal : Blood. 2009 Jul 9;114(2):469-77. Epub 2009 May 13.
Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis.
Specimen part
View SamplesEscherichia coli (E. coli) amine oxidase (ECAO) encoded by tynA gene has been one of the model enzymes to study the mechanism of oxidative deamination of
Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate.
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View SamplesMolecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia.
Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia.
Sex, Age, Specimen part
View SamplesGlioblastoma (GBM) patient-derived orthotopic xenografts (PDOXs) were derived from organotypic spheroids obtained from patient tumor samples. To detect whether gene expression profiles of GBM patient tumors are retained in PDOXs, we performed genome-wide transcript analysis by human-specific microarrays . In parallel, we analyzed GBM cell cultures and corresponding intracranial xenografts from stem-like (NCH421k, NCH644) and adherent GBM cell lines (U87, U251). PDOXs show a better transcriptomic resemblance with patient tumors than other preclinical models. The major difference is largely explained by the depletion of human-derived non-malignant cells.
Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology.
Specimen part, Disease
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