Murine healthy tissue samples, DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas.
Identification of early molecular markers for breast cancer.
Specimen part
View SamplesHuman healthy tissue samples, DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas.
Identification of early molecular markers for breast cancer.
Specimen part, Disease, Disease stage
View SamplesHere, we report on experiments in double-transgenic mice, in which RFP is expressed in all Foxp3+ Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFP) origin in otherwise unmanipulated mice.
Fluorochrome-based definition of naturally occurring Foxp3(+) regulatory T cells of intra- and extrathymic origin.
No sample metadata fields
View SamplesHIF-1 is an important transcription factor for immune responses to bacterial infection. We wanted to analyze the HIF-1 dependent gene expression upon S. aureus infection and analyzed the gene expression of HepG2 nt and HepG2 HIF-1-/- cells four hours upon infection using affymetrix human gene 1.0 st. gene arrays.
Hypoxia-inducible factor 1-regulated lysyl oxidase is involved in Staphylococcus aureus abscess formation.
Specimen part
View SamplesMicrotubule actin crosslinking factor 1 (Macf1) plays a role in coordinated actions of actin and microtubules in multiple cellular processes. Here we show that Macf1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of Macf1 in adult photoreceptors caused reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for Macf1 function. Macf1 was also shown to interact with ciliary proteins Mkks and Talpid3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking Macf1, and that Mkks and Talpid3 are involved in the coordination of microtubule and actin interactions. Overall design: RNA was isolated from confluent mouse embryonic fibroblasts (3 clones per genotype). MEFs where generated from Macf1flox/flox and Macf1flox/+ mice, and immortalized via transfection with the SV40 large T antigen. Cells were grown to 75% confluency and treated with AAV8-CMV-Cre (1.2x10e13vg/ml) overnight. Single cell colonies were generated and recombination for the Macf1 knockout allele (Macf1-/-) and heterozygous control (Macf1-/+) was confirmed by sequencing. Loss of protein expression was confirmed by western blot. Cells were grown to confluency and serum starved on gelatin coated glass coverslips prior to fixing and immunostaining as described for the retina.
Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.
Specimen part, Subject
View SamplesConstitutive low level DNA damage is linked to innate immune activation. Hierarchical clustering of over 9000 transcripts revealed remarkably similar profiles in a patient with lupus erythematosus and a patient with AGS with up-regulation of genes involved in DNA damage signaling, p53-inducible genes, senescence-associated genes as well as up-regulation of interferon-stimulated genes. Transcriptional profiling of fibroblasts exposed to oxidative stress showed a marked up-regulation of genes involved in DNA replication/repair and replication licensing in TREX1-deficient cells compared to wild type cells suggesting massive replication stress. Overall design: Comparison of transcriptional profiles of unstressed patient fibroblasts with wild type cells as well as fibroblasts exposed to oxidative stress
RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA.
No sample metadata fields
View SamplesWe investigated at which stage of maturation commitment to a stable Foxp3-expressing phenotype takes place. We assessed stability of Foxp3 expression in thymic Foxp3+ Treg subsets of different maturity, defined by CD24 expression. Next we compared gene expression profiles of Foxp3+ Treg subsets (+) of different maturity (24lo, 24int, 24hi) and could identify a set of genes that were specifically up or downregulated in Foxp3+ Tregs, but not in Foxp3- conventional T cells, in a maturation-dependent manner.
Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus.
Specimen part
View SamplesWe aimed to characterize the complex cardiovascular effects of NOsGC stimulation using NO-independent stimulator BAY 41-8543 in a double transgenic rat (dTGR) model of HFpEF.
Nitric oxide-sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction.
Sex, Specimen part, Treatment
View SamplesDuring development, thymocytes bearing a moderately self-reactive T cell receptor (TCR) can be selected to become regulatory T (Treg) cells. Several observations suggest that also in the periphery mature Treg cells continuously receive self-reactive TCR signals. However, the importance of this inherent autoreactivity for Treg cell biology remains poorly defined.
Continuous T cell receptor signals maintain a functional regulatory T cell pool.
Specimen part
View SamplesROR?t is a transcription factor required for T helper 17 (Th17) cell development. We identified three ROR?t-specific inhibitors that suppress Th17 cell responses including Th17 cell-mediated autoimmune disease. We systemically characterized ROR?t binding data in the presence and absence of drug with corresponding whole-transcriptome sequencing for wild-type and ROR?t-deficient cells. ROR?t is central in a densely interconnected regulatory network, acting both as a direct activator of genes important for Th17 cell differentiation and as a direct repressor of genes from other T-cell lineages. The three inhibitors identified here reversed both of these modes of action, but to varying extents and through distinct mechanisms. Whereas one inhibitor displaced ROR?t from its target-loci, the two more potent inhibitors affected transcription predominantly without removing DNA-binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity. Overall design: Transcriptional profiling of Th17 cells under chemical perturbations of ROR?t, DMSO, and knockout of ROR?t. It includes repeats for all the data in GSE56018, plus one additional condition.
Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms.
No sample metadata fields
View Samples