Abstract: During Drosophila oogenesis, germline stem cell (GSC) identity is maintained largely by preventing the expression of factors that promote differentiation. This is accomplished via the activity of several genes acting either in the GSC or its niche. The translational repressors, Nanos and Pumilio, act in GSCs to prevent differentiation, likely by inhibiting translation of early differentiation factors, while niche signals prevent differentiation by silencing transcription of the differentiation factor Bam. We have found that the DNA-associated protein Stonewall (Stwl) is also required for GSC maintenance. stwl is required cell-autonomously; clones of stwl- germ cells were lost by differentiation, and ectopic Stwl caused an expansion of GSCs. stwl mutants acted as Suppressors of Variegation, indicating stwl normally acts in chromatin-dependent gene repression. In contrast to several previously described GSC maintenance factors, Stwl likely functions epigenetically to prevent GSC differentiation. Stwl-dependent transcriptional repression does not target bam, but rather Stwl represses the expression of many genes, including those that may be targeted by Nanos/Pumilio translational inhibition.
Stonewalling Drosophila stem cell differentiation by epigenetic controls.
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Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis.
Sex, Age, Specimen part
View SamplesRationale: The fibrosing idiopathic interstitial pneumonias (IIPs) are classified based on clinical, radiographic, and pathologic criteria. The separation into phenotypic subgroups is useful in predicting outcome and therapeutic strategy; however a large degree of ambiguity remains. Gene expression profiling may contribute to traditional criteria in IIPs by characterizing the dynamic biology that more accurately distinguishes subtypes of these diseases or their prognoses.
Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis.
Sex, Age, Specimen part
View SamplesThe transcriptional events accompanying synaptogenesis are largely unknown, or have been studied in systems in which synapse formation occurs gradually over time. With a system in which synaptogenesis is synchronized and controllable, molecular or biochemical techniques can be used to examine cellular events across cultures on a wide scale, as synapses develop.
Synaptogenesis in purified cortical subplate neurons.
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View SamplesWe developed a 5''RNA-seq methodology to concurrently assess gene expression and start-site usage changes. We applied this methodology to study hypertrophic cardiomyopathy in mice harboring a human deleterious mutation. Overall design: 5''RNA-seq analysis of transcriptomes from mouse hearts with or without hypertrophic cardiomyopathy. Biological replicates were pooled into a single sequencing run. 5''RNA-seq methodology consists of enhanced sequencing of 5'' ends and computational assessment of changes at start-sites of genes.
5'RNA-Seq identifies Fhl1 as a genetic modifier in cardiomyopathy.
No sample metadata fields
View SamplesThe aim of this study was to employ a systems-level analysis to elucidate gene expression networks operating in the CD4 T-cell responses which underpin human atopic disease.
A network modeling approach to analysis of the Th2 memory responses underlying human atopic disease.
Time
View SamplesWhile prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular.
Transcriptomic responses to prion disease in rats.
Specimen part, Disease
View SamplesDendritic cells differentiate from their precursors in the airway mucosa under local environmental instruction. Airway epithelial cells (AEC) are a potent source of both pro- and anti-inflammatory mediators and are in intimate contact with intraepithelial DC and their precursors. Thus, AEC are likely candidates for influencing this differentiation process in order to tailor the DC for optimal function in the airway mucosa.
Airway epithelial cells regulate the functional phenotype of locally differentiating dendritic cells: implications for the pathogenesis of infectious and allergic airway disease.
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View SamplesMice lacking the transcription factor Fezf1 exhibit defects in the structural and molecular organiztion of their olfactory system. To invetigate this at the level of gene expression, we isolated Fezf1 expressing cells by FACS from the MOE of Fezf1+/- or Fezf1-/- animals and compared their gene expression profiles.
Fezf1 and Fezf2 are required for olfactory development and sensory neuron identity.
Specimen part
View SamplesPseudomonas aeruginosa is an opportunistic pathogen that can adapt to changing environments and can secrete an exopolysaccharide known as alginate as a protection response resulting in a colony morphology and phenotype referred to as mucoid. However how P. aeruginosa senses its environment and activates alginate overproduction is not fully understood. Previously, we showed that Pseudomonas isolation agar (PIA) supplemented with ammonium metavanadate (PIAAMV) induces P. aeruginosa to overproduce alginate. Vanadate is a phosphate mimic and causes protein misfolding by disruption of disulfide bonds. Here we used PIAAMV to characterize the pathways involved in inducible alginate production and tested the global effects of P. aeruginosa growth on PIAAMV by a mutant library screen, transcriptomics, and in a murine acute virulence model. The PA14 non-redundant mutant library was screened on PIAAMV to identify new genes that are required for the inducible alginate stress response. A functionally diverse set of genes encoding products involved in cell envelope biogenesis, peptidoglycan, uptake of phosphate and iron, phenazines biosynthesis, and other processes were identified as positive regulators of the mucoid phenotype on PIAAMV. Transcriptome analysis of P. aeruginosa growing in the presence of vanadate caused differential expression of genes involved in virulence, envelope biogenesis, and cell stress pathways. In this study, it was observed that growth on PIAAMV attenuates P. aeruginosa in a mouse pneumonia model. Induction of alginate overproduction occurs as a stress response to protect P. aeruginosa but it may be possible to modulate and inhibit these pathways based on the new genes identified in this study.
Genes required for and effects of alginate overproduction induced by growth of Pseudomonas aeruginosa on Pseudomonas isolation agar supplemented with ammonium metavanadate.
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