The Epidermal Growth Factor Receptor (EGFR)/ligand system is centrally involved in multiple homeostatic functions of the epithelia. Epithelial cells are the primary targets of humanized antibodies and small molecule inhibitors against this system, whereby the constellation of skin-specific side effects of these drugs stems from a profound disturbance of keratinocyte biology. So far, the molecular mechanisms underlying these toxic events have been investigated only broadly. Here we show that keratinocyte response to anti-EGFR drugs comprises the development of a type 1 interferon (IFN) molecular signature including enhanced expression of IFN-kappa. Mechanistically, nuclear accumulation of IRF1 precedes this signature as well as the enhanced expression of a chemokine cluster we previously identified as a relevant pro-inflammatory component of EGFR inhibition. In fact, either silencing of IRF1 transcript expression, or antibody-mediated blockade of type 1 IFN receptor function and consequent abrogation of STAT1 activation, leads to impairment of this gene transcription profile. High levels of IRF1 and IFN-kappa can be clearly observed in the early skin lesions of patients treated with cetuximab. Type 1 IFN signaling could be crucially implicated in the triggering of the inflammatory mechanisms active in the skin of patients under treatment with anti-EGFR drugs.
Epidermal growth factor receptor inhibitors trigger a type I interferon response in human skin.
Specimen part, Cell line
View SamplesThe comparison of trancriptomes was part of the study by Pasternak et al. The goal was to check if BTG4 regulates mRNA polyadenylation during mouse oocyte meiosis. To test this we compared the abundancies of the polyadenylated trancripts in control and Btg4-depleted oocytes. Overall design: 3 samples of 50 oocytes were collected for both groups
The BTG4 and CAF1 complex prevents the spontaneous activation of eggs by deadenylating maternal mRNAs.
Cell line, Subject
View SamplesmRNA expression data were collected from patients with brain tumor to improve diagnostic of gliomas on molecular level.
Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain.
No sample metadata fields
View SamplesWe investigated the occupancy of RNA PolII and INTS11 during the stimulation of EGF and compared with drug treated condition using inhibitors against MAPK pathway and Integrator. Additionally, we examined transcription by sequencing the chromatin-bound fraction of RNA. Overall design: We employed several cel lines in our experiment, including HELA, KRAS mutant lung cancer cell line A549 and BRAF mutatant melanoma cell line A375. The conditons we checked including EGF stimulation, MAPK pathway inhibition using BRAF, MEK or ERK inhibitiors, targeting INTS11 with RNAi or integrator inhibitor. We used RNA sequencing to measure the expression profile and CHIP sequencing to detect INTS11 and RNA PolII recruitment on chromatin.
Integrator orchestrates RAS/ERK1/2 signaling transcriptional programs.
No sample metadata fields
View SamplesThe comparison of trancriptomes was part of the study by Pfender, Kuznetsov, Pasternak et al, titled: "Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes". The goal was to check if the oocytes cultured in vitro in follicles (for RNAi studies) correspond to real gametes obtained directly from mice (in vivo). Apart from functional experiments showing that they can be fertilized and develop into an embryo, we also compared transcriptomes of those oocytes. Overall design: 3 samples of 50 oocytes were collected for both groups of in vitro and in vivo grown oocytes.
Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes.
No sample metadata fields
View SamplesIn the present study, the transcriptional analysis of CD biopsies reveals profound alterations in the ileum transportome profile. More than 60 SLC transporters showed different expression pattern compared with the healthy donors, being mostly decreased. Changes were confirmed in almost all the eighteen altered SLCs analyzed by RT-PCR. The results obtained display alterations in amino acid transporters, purinome members, Zn transporters and metallothioneins. All together, these alterations which mainly involve transporters localized at the apical membrane of the enterocyte anticipate impaired amino acid uptake and purinergic responses. Remarkably, incubation of explants with specific commensal bacteria restored almost all CD transportome alterations.
Transportome Profiling Identifies Profound Alterations in Crohn's Disease Partially Restored by Commensal Bacteria.
Specimen part, Disease
View SamplesThe ability to detect and isolate bGL1-22/LGL1specific human type II NKT cells allowed us to compare the global gene expression profiles of these cells with type I NKT cells using microarray analysis. Principal component analysis revealed that the gene expression profile signature for bGL1-22 and LGL1-specific T cells both before and after activation with anti-CD3/CD28 beads is distinct from that of type I NKT cells.
Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation.
Specimen part
View SamplesTransgenic PiZ mice have been genetically engineered to express ATZ and have been a valuable experimental model for studing liver disease associated with AAT deficiency. ATZ accumulates in these mice within the ER of hepatocytes in a nearly identical manner to livers of affected patients. To investigate the pathogenesis of liver damage induced by ATZ, we performed gene expression analysis in livers of 6-week-old PiZ mice and strain-, age-, and gender-matched wild-type mouse controls. All samples were processed on Affymetrix Mouse 430A 2.0 arrays using GeneChip 3-IVT Plus and Hybridization Wash and Stain kits by means of Affymetrixs standard protocols. The analysis indicated that most genes upregulated in PiZ livers were associated with response to unfolded proteins, ER nuclear signaling pathway, and response to protein stimulus.
Activation of the c-Jun N-terminal kinase pathway aggravates proteotoxicity of hepatic mutant Z alpha1-antitrypsin.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.
Specimen part, Disease, Disease stage, Cell line, Treatment
View SamplesA majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Our study evaluates the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease.
Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.
Specimen part, Disease, Disease stage
View Samples