We are daily exposed to a multitude of health hazardous airborne particulate matter with notable deposition in the fragile alveolar region of our lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modelling, we have here determined that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows us to predict the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modelling potentially relating outcomes to material properties for large number of materials thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, our work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives.
Prediction of Chronic Inflammation for Inhaled Particles: the Impact of Material Cycling and Quarantining in the Lung Epithelium.
Cell line
View SamplesCTCF is a multifunctional nuclear factor involved in epigenetic regulation. We have used transgenic RNA interference to deplete maternal stores of CTCF from growing mouse oocytes, and identified the potential target genes
Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development.
No sample metadata fields
View SamplesAs the most widely used mammalian model organism, mice play a critical role in biomedical research for mechanistic study of human development and diseases. Today, functional sequences in the mouse genome are still poorly annotated a decade after its initial sequencing. We report here a map of nearly 300,000 cis-regulatory sequences in the mouse genome, representing active promoters, enhancers and CTCF binding sites in a diverse set of 19 tissues and cell types. This map provides functional annotation to nearly 11% of the genome, and over 70% of conserved, non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we demonstrate that cis-regulatory sequences are organized into domains of coordinately regulated enhancers and promoters. Our results provide a valuable resource for the annotation of functional elements in the mammalian genome, and study of regulatory mechanisms for tissue-specific gene expression. Overall design: 19 tissues and primary cell types were examined.
A map of the cis-regulatory sequences in the mouse genome.
No sample metadata fields
View SamplesMissense mutations in the gene for the ubiquitously expressed superoxide dismutase-1 (SOD1) are one of the causes of familial amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disease in humans killing selectively large motor neurons. Mice and rats overexpressing mutant SOD1 develop an adult onset neurodegenerative disease with hindlimb-paralysis and subsequent death similar to the human condition. In order to analyze the effects of mutant SOD1 expression onto the most affected cell-type in ALS, a small subpopulation of spinal cord cells, we propose to use laser microdissection to isolate mouse lumbar motor neurons and to assess the changes onto the mRNA expression profile using Affymetrix GeneChips compared to control animals. While two studies applying a genomic approach on the ALS mouse models used the entire spinal cord, contributions of changes to motor neurons were masked by the inflammatory effects of mutant SOD1 and the much larger population of non-motor neuronal cells. What is therefore needed is a cell-type specific expression profile that could reveal dysregulations in the transcriptome of the affected motor neurons.
Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons.
No sample metadata fields
View SamplesThe goals of this study are to define the putatitve impacts of FXRalpha deficiency in testicular physiology Overall design: Testis mRNA profiles of 10-day old wild type (WT) and FXralpha-/- mice were generated by deep sequencing, on 5 individual mice for each geneotype, sequence on flowcell HS168.
The Bile Acid Nuclear Receptor FXRα Is a Critical Regulator of Mouse Germ Cell Fate.
Specimen part, Cell line, Subject
View SamplesDepolarization of resting membrane potential in select cells in Xenopus larvae induces striking hyperpigmentation due to dysregulation of melanocytes. Here, we show that this non-cell-autonomous process is mediated by cAMP, CREB, and the transcription factors Sox10 and Slug. Our microarray analysis reveals specific transcripts responsive to Vmem levels within a few hours of depolarization, and a set of 517 transcripts whose expression remains altered during the full hyperpigmented phenotype over a week later, linking instructor cell-depolarization to a range of developmental processes and disease states. We also show that voltage-dependent conversion of melanocytes involves the MSH-secreting melanotrope cells of the pituitary, and formulate a model for the molecular pathway linking the bioelectric properties of melanocyte cells microenvironment in vivo to the genetic and cellular changes induced in this melanoma-like phenotype. Remarkably, the phenotype is all-or-none: each individual animal either undergoes melanocyte conversion or not, as a whole. This group decision is stochastic, resulting in varying percentages of hyperpigmented individuals for a given experimental treatment. To understand the stochasticity and dynamic properties of this complex signaling system, we developed a novel computational method that automates the reverse-engineering of stochastic dynamic signaling models. We used this method to discover a network model that quantitatively explained our complex dataset, and even made correct predictions for new experiments that we validated in vivo. Taken together, these data (1) reveal new molecular details about a novel trigger of metastatic-like developmental cell behavior in vivo, (2) suggest new targets for biomedical intervention, and (3) demonstrate proof-of-principle of a computational method for understanding stochastic decision-making by cells during embryonic development and metastasis.
Serotonergic regulation of melanocyte conversion: A bioelectrically regulated network for stochastic all-or-none hyperpigmentation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Serially transplantable mammary epithelial cells express the Thy-1 antigen.
Specimen part
View SamplesEnriched cell populations from murine mammary epithelium were isolated by FACS and subjected to Affymetrix Mouse 430 2.0 microarray analysis.
Serially transplantable mammary epithelial cells express the Thy-1 antigen.
Specimen part
View SamplesEnriched cell populations from murine mammary epithelium were isolated by FACS and subjected to Affymetrix Mouse 430 2.0 microarray analysis.
Serially transplantable mammary epithelial cells express the Thy-1 antigen.
Specimen part
View SamplesTissue samples were collected from patients diagnosed with HNSCC (oropharynx, hypopharynx, larynx). Samples were taken from the tumor site (tumor samples) and from a site distant to the tumor (normal samples) prior to therapy.
Prognostic biomarkers for HNSCC using quantitative real-time PCR and microarray analysis: β-tubulin isotypes and the p53 interactome.
Age, Specimen part, Subject
View Samples