For up to 70 weeks we subcutaneuously injected two hundered p53R270HWAPCre mice to different insulin-like molecules (regular insulin, insulin glargine, insulin X10 (of AspB10), IGF1 or vehicle solution). Due to the mammary gland specific p53 mutation the p53R270HWAPCre mice will develop spontanously human like mammary gland tumors in about a year. We found that frequent injections to insulin like molecules decreased the mammary gland tumor latency time in this model. Next we mRNA seqeunced tumors to reveal the underlying mechanisms for the increased tumor progression. For the next generation experiment we isolated mRNA from 50 tumors (10 tumors of each stimulation group) and sequenced with the IonTorrent (40 mil reads, on average 100 bp reads) Overall design: RNA expression profiles of 50 mammary gland tumors were analyzed, 10 tumors per treatment group (chronic insulin, glargine, x10, IGF1 or vehicle exposure)
Insulin-like growth factor 1 receptor activation promotes mammary gland tumor development by increasing glycolysis and promoting biomass production.
Specimen part, Cell line, Subject
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Gene Array Analyzer: alternative usage of gene arrays to study alternative splicing events.
Age, Specimen part
View SamplesThe latest version of microarrays released by Affymetrix, the GeneChip Gene 1.0 ST Arrays (gene arrays), are designed in a similar fashion as exon arrays, which enables to identify differentially expressed exons, rather than only the expression level of whole transcripts. Here, we propose an extension, Gene Array Analyzer (GAA), to our previously published Exon Array Analyzer (EAA). GAA enables to analyse gene arrays on exon level and therefore supports to identify alternative splicing with gene arrays. To show the applicability of GAA, we used gene arrays to profile alternative splice events during the development of the heart. Further re-analysis of published gene arrays could show, that some of these splice events reoccur under pathological conditions. The web interface of GAA is user friendly, functional without set up and freely available at http://GAA.mpi-bn.mpg.de.
Gene Array Analyzer: alternative usage of gene arrays to study alternative splicing events.
Age, Specimen part
View SamplesThe human hair follicle bulge is an important niche for keratinocyte stem cells (KSC). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSC. In this study, we determined the distribution of label-retaining cells to carefully define the human anagen bulge. Using navigated-laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and Activin/BMP signaling were over-represented in the bulge while genes responsible for cell proliferation were under-represented, consistent with quiescent non-cycling KSC in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1 while CD24, 34, 71 and 146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hi24lo34lo71lo146lo) obtained from hair follicle suspensions demonstrated high colony forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells.
Characterization and isolation of stem cell-enriched human hair follicle bulge cells.
No sample metadata fields
View SamplesMalignant gliomas constitute one of the most significant areas of unmet medical need, due to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We found that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated to invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a crtitical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signaling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signaling. Overall design: Transcriptomic analysis of two different stages of gliomagenesis
Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.
No sample metadata fields
View SamplesAllergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including miRNAs, are pivotal in maintaining immune-homeostasis. Since an altered expression of various miRNAs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRNAs control mechanisms ensuring Th2 stability and maintenance in the lung. We isolated murine CD4+ Th2 cells from allergic inflamed lungs and profiled gene and microRNA expression.
A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Age, Specimen part, Treatment, Subject, Time
View SamplesThe carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. For insight into early mechanisms of non-genotoxoc carcinogenesis and for identification of potential early biomarkers of non-genotoxic carcinogenesis, groups of rats were treated with a range of known non-genotoxic carcinogens for a period of 14, 28, or 90 days, and liver tissue was harvested for expression profiling. Control groups were treated with appropriate vehicles.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment, Subject
View Samples