Irritant contact dermatitis (ICD) pathogenesis is not completely understood and the genes participating in the epidermal response towards chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies (, 4 and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to sodium lauryl sulphate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays revealed essentially different pathway responses h after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen activated signalling cascades including ERK and growth factor receptor signalling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed while 26 suggested common biomarkers were identified . In conclusion, we bring new insights into two hitherto less well elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative exposure, respectively.
Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.
Specimen part
View SamplesGene expression profiling is a promising diagnostic and prognostic tool. Expression profiles are snap-shots of mRNA levels at time of extraction and they have been shown to be affected by tissue handling during sample collection. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing has been described in a number of studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery.
Differential effect of surgical manipulation on gene expression in normal breast tissue and breast tumor tissue.
Sex, Specimen part, Disease, Subject
View SamplesWe used microarrays to assess gene expression in patients with ET, PV, and PMF compared to control subjects
Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis.
Specimen part, Disease
View SamplesInsulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZD) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZD in PCOS is in part mediated by changes in the transcriptional profile of muscle favoring insulin sensitivity.
Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome.
No sample metadata fields
View SamplesTo obtain a separation of the epidermal and dermal compartments in order to examine compartment specific biological mechanisms in the skin we incubated 4 mm human skin punch biopsies in ammonium thiocyanate (NH4SCN). We wanted to test 1) the histological quality of the dermo-epidermal separation obtained by different incubation times 2) the amount and quality of extractable epidermal RNA, and 3) its impact on sample RNA expression profiles assessed by large-scale gene expression microarray analysis in both normal and inflamed skin. At 30 minutes incubation, the split between dermis and epidermis was not always histologically well-defined (i.e. occurred partly intra-epidermally) but varied between subjects. Consequently, curettage along the dermal surface of the biopsy was added to the procedure. This modified method resulted in an almost perfect separation of the epidermal and dermal compartments and satisfactory amounts of high-quality RNA were obtained. Hybridization to Affymetrix HG_U133A 2.0 GeneChips showed that ammonium thiocyanate incubation had a minute effect on gene expression resulting in only one significantly downregulated gene (cystatin E/M). We conclude that epidermis can be reproducibly and almost completely separated from the dermis of 4 mm skin biopsies by 30 min incubation in 3.8% ammonium thiocyanate combined with curettage of the dermal surface, producing high-quality RNA suitable for transcriptional analysis. Our refined method of dermo-epidermal separation will undoubtedly prove valuable in the many different settings, where the epidermal and dermal compartments need to be evaluated separately.
Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies.
Specimen part, Subject
View SamplesMicroarrays were used to assess gene expression in patients with ET, PV, and PMF before and after treatment with IFNalpha2 in a paired design.
The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms.
Specimen part, Disease, Disease stage, Treatment
View SamplesMicroarrays were used to assess gene expression in patients with ET, PV, and PMF before treatment with IFNalpha2.
Whole blood transcriptional profiling reveals deregulation of oxidative and antioxidative defence genes in myelofibrosis and related neoplasms. Potential implications of downregulation of Nrf2 for genomic instability and disease progression.
Specimen part, Disease, Disease stage, Treatment
View SamplesRecently, abnormalities in mitochondrial oxidative phosphorylation (OXPHOS) have been implicated in the pathogenesis of skeletal muscle insulin resistance in type 2 diabetes. In the present study, we hypothesized that decreased expression of OXPHOS genes could be of similar importance for insulin resistance in the polycystic ovary syndrome (PCOS).
Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome.
No sample metadata fields
View SamplesTo gain insight in the kinetics and interplay of the predominant transcriptional responses of DNA damage signalling pathways in undifferentiated cells, mouse embryonic stem cells were exposed to cisplatin at four different time points (2, 4, 8 and 24 hr) and concentrations (1, 2, 5 and 10 uM). RNA was isolated and subjected to genome-wide expression profiling.
A portrait of cisplatin-induced transcriptional changes in mouse embryonic stem cells reveals a dominant p53-like response.
Specimen part, Compound, Time
View SamplesIn contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located at the wound border. Here, we show that tomo-seq can be used to identify whole-genome transcriptional profiles of the injury zone, the border zone and the healthy myocardium. Interestingly, the border zone is characterized by the re-expression of embryonic cardiac genes that are also activated after myocardial infarction in mouse and human, including targets of Bone Morphogenetic Protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts. Overall design: To generate spatially-resolved RNA-seq data for injured zebrafish hearts (3 and 7 days-post-injury), we cryosectioned samples, extracted RNA from the individual sections, and amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing.
Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration.
Specimen part, Subject
View Samples