Although host genetics influences susceptibility to tuberculosis, few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of tuberculosis infection would have distinct gene expression profiles, and that polymorphisms in these genes may also be associated with susceptibility to TB.
Identification of tuberculosis susceptibility genes with human macrophage gene expression profiles.
No sample metadata fields
View SamplesThe X-linked DDX3X gene encodes an ATP-dependent DEAD-box RNA helicase frequently altered in various human cancers including melanomas. Despite its important roles in translation and splicing, how DDX3X dysfunction specifically rewires gene expression in melanoma remains completely unknown. Here we uncover a DDX3X-driven post-transcriptional program that dictates melanoma phenotype and poor disease prognosis. Through an unbiased analysis of translating ribosomes we identified the microphtalmia-associated transcription factor, MITF, as a key DDX3X translational target that directs a proliferative-to-metastatic phenotypic switch in melanoma cells. Mechanistically, DDX3X controls MITF mRNA translation via an internal ribosome entry site (IRES) embedded within the 5' untranslated region. Through this exquisite translation-based regulatory mechanism, DDX3X steers MITF protein levels dictating melanoma metastatic potential in vivo and response to targeted therapy. Together these findings unravel a post-transcriptional layer of gene regulation that may provide a unique therapeutic vulnerability in aggressive male melanomas. Overall design: We sequenced transcripts associated with translationally active ribosomes (polysomes) isolated by sucrose gradient fractionation from DDX3X and control siRNA-transduced HT144 cells. Experiments were performed in duplicates.
The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma.
Specimen part, Cell line, Subject
View SamplesThe objective of the present study was to identify genes that are involved in increasing the ovulation number in mouse line FL1 that had been selected for high fertility performance.
Expression profiling of a high-fertility mouse line by microarray analysis and qPCR.
No sample metadata fields
View SamplesMetabolic, mitochondrial and behavioral correlations with transcriptional profiles from the CA1 and DG hippocampal regions of young and aged rhesus macaque. Increasing evidence indicates that obesity correlates with impaired cognitive performance during normal aging and is a major risk factor for Alzheimers disease. However, little is known regarding how peripheral metabolic variables affect cellular pathways in brain regions important for memory. Brain inflammation, mitochondrial dysregulation, and altered transcriptional regulation have all been found to occur with aging, and recent microarray analyses in rodent models have linked these processes and others to age-related memory impairment. However, whether these brain changes are also associated with metabolic variables is not known. Aging monkeys exhibit several metabolic changes similar to those seen in humans. Here, we tested peripheral-brain relationships in six young (7.0 +/- 0.3 years) and six aged (23.5 +/- 0.7 years) female rhesus monkeys. Animal cognition was gauged with a variable delay task; blood constituents were assessed with a serum chemistry panel emphasizing markers of metabolic dysfunction; mitochondrial function was measured from the hippocampus of one hemisphere; and the CA1 and dentate gyrus regions of the other hippocampus were dissected out for gene expression microarray analysis. Aged animals showed reduced performance on the behavioral task, exhibited aspects of metabolic dysregulation including increased insulin, triglyceride, and chylomicron levels (consolidated into a peripheral metabolic index), and showed a significant age-related reduction in State III oxidation, a measure of mitochondrial function. Microarray analyses revealed hundreds of genes that correlated with the peripheral metabolic index. However, DAVID statistical pathway analyses showed that upregulated inflammatory genes in CA1 and downregulated transcriptional regulation genes in dentate gyrus and CA1 were particularly overrepresented among genes correlated with the peripheral index. Thus, the association of metabolic variables with specific neuropathological processes in different regions of the hippocampal formation may have implications for mechanisms through which peripheral metabolism alters the risk for Alzheimers disease.
Aging-related gene expression in hippocampus proper compared with dentate gyrus is selectively associated with metabolic syndrome variables in rhesus monkeys.
No sample metadata fields
View SamplesWe demonstrate that transcriptomic profiling of the NER mutant ercc-1 offers better understanding of the complex phenotypes of ercc-1 deficiency in C. elegans, as it does in mammalian models. There is a transcriptomic shift in ercc-1 mutants that suggests a stochastic impairment of growth and development, with a shift towards a higher proportion of males in the population. Extensive phenotypic analyses confirm that NER deficiency in C. elegans leads to severe developmental and growth defects and a reduced replicative lifespan, although post-mitotic lifespan is not affected. Results suggest that these defects are caused by an inability to cope with randomly occurring DNA damage, which may interfere with transcription and replication.
DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expansion of multipotent stem cells from the adult human brain.
Sex, Age, Specimen part
View SamplesTissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Expansion of multipotent stem cells from the adult human brain.
Sex, Age, Specimen part
View SamplesTissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Expansion of multipotent stem cells from the adult human brain.
Sex, Age, Specimen part
View SamplesTissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Expansion of multipotent stem cells from the adult human brain.
Sex, Age, Specimen part
View SamplesTissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Expansion of multipotent stem cells from the adult human brain.
Sex, Age, Specimen part
View Samples