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GSE75676
Homo sapiens
7 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of Circulating Fibrocytes and Dendritic Derivatives in Corneal Endothelium of Patients With Fuchs' Dystrophy.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a degenerative eye disorder affecting 4% of Americans older than 40. It is the leading indication for corneal endothelial (CE) transplantation for which there is a global donor shortage. This study aimed to gain further insight into the pathophysiology of FECD and identify targets for nonsurgical therapy.
Publication Title
Identification of Circulating Fibrocytes and Dendritic Derivatives in Corneal Endothelium of Patients With Fuchs' Dystrophy.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We compared expression of genes in brains of SIRT1 brain-specific knockouts (BSKO) to those of wild-type littermate controls (WT).
Publication Title
SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study, we studied chronic HCV patients who responded to IFN-based therapy as evidenced by absence of HCV RNA at the end of treatment, and focused on two issues that have not received much attention. Firstly, we evaluated whether specific genes or gene expression patterns in blood were able to distinguish responder patients with a viral relapse from responder patients who remained virus-negative after cessation of treatment. We found that chronic HCV patients who were sustained responders and relapsers to IFN-based therapy showed comparable baseline clinical parameters and immune composition in blood. However, at baseline, the gene expression profiles of a set of 18 genes predicted treatment outcome with an accuracy of 94%. Secondly, we examined whether patients with successful therapy-induced clearance of HCV still exhibited gene expression patterns characteristic for HCV, or whether normalization of their transcriptome was observed. We observed that the relatively high expression of IFN-stimulated genes (ISG) in chronic HCV patients prior to therapy was reduced after successful IFN-based antiviral therapy (at 24 weeks follow-up). These ISG included CXCL10, OAS1, IFI6, DDX60, TRIM5 and STAT1. In addition, 1428 differentially expressed non-ISG genes were identified in paired pre- and post-treatment samples from sustained responders, which included genes involved in TGF- signaling, apoptosis, autophagy, and nucleic acid and protein metabolism. Interestingly, 1424 genes were identified with altered expression in responder patients after viral eradication in comparison to normal expression levels in healthy individuals. Additionally, aberrant expression of a subset of these genes, including IL-32, IL-16, CCND3 and RASSF1, was also observed at baseline. Our findings indicate that successful antiviral therapy of chronic HCV patients does not lead to normalization of their blood transcriptional signature. The altered transcriptional activity may reflect HCV-induced liver damage in previously infected individuals.
Publication Title
Gene expression profiling to predict and assess the consequences of therapy-induced virus eradication in chronic hepatitis C virus infection.
Sample Metadata Fields
Sex, Specimen part, Disease, Race
View Samples- Homo sapiens
- 437 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Purpose: Severe late normal tissue damage limits radiotherapy treatment regimens. This study aims to validate -H2AX foci decay ratios and induced expression levels of DNA double strand break (DSB) repair genes, found in a retrospective study, as possible predictors for late radiation toxicity. Methods and Materials: Prospectively, decay ratios (initial/residual -H2AX foci numbers) and genome-wide expression profiles were examined in ex vivo irradiated lymphocytes of 198 prostate cancer patients. All patients were followed 2 years after radiotherapy, clinical characteristics were assembled and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. Results: No clinical factors were correlated with late radiation toxicity. Analysis of -H2AX foci uncovered a negative correlation between the foci decay ratio and toxicity grade. Significantly smaller decay ratios were found in grade3 compared to grade 0 patients (p=0.02), indicating less efficient DNA-DSB repair in radio-sensitive patients. Moreover, utilizing a foci decay ratio threshold determined in our previous retrospective study correctly classified 23 of the 28 grade3 patients (sensitivity, 82%) and 9 of the 14 grade 0 patients (specificity, 64%). Grade of toxicity also correlated with a reduced induction of the homologous recombination (HR) repair gene-set. The difference in average fold induction of the HR gene-set was most pronounced between grade 0 and grade3 patients (p=0.008). Conclusions: Reduced responsiveness of HR repair genes to irradiation and inefficient DSB repair correlate with an increased risk of late radiation toxicity. Using a decay ratio classifier, we could correctly classify 82% of the patients with grade3 toxicity. Additional studies are required to further optimize and validate the foci decay assay and to assess its predictive value for late radiation toxicity in patients prostate cancer
Publication Title
Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
C/EBPalpha is a transcription factor critically involved in myeloid development and indispensable for formation of granulocytes. To track the cellular fate of stem and progenitor (LSK) cells, which express C/EBPalpha, we developed a mouse model expressing Cre recombinase from the Cebpa promoter and an inducible EYFP allele. We show that Cebpa/EYFP+ cells represent a significant subset of LSK cells, which predominantly give rise to myeloid cells in steady state hematopoiesis.
Publication Title
Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
Illumina HiSeq 2500
Description
Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P=6.2x10-13), including Atf3 (P=2.4x10-41), Penk (P=1.3x10-15), and Kcnq3 (P=3.1x10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory. Overall design: Biological replicates: Fear conditioned: n=14, No shock controls: n=4, Home cage controls:n=3. The contents 10 dVenus+ and 10 dVenus- cells were aspirated from each animal (biological replicate)
Publication Title
Engram-specific transcriptome profiling of contextual memory consolidation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- NextSeq 500
Description
The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury. Overall design: We generated transciptome data from proliferative cardiac cells collected from 3, 7 or 14 days following myocardial infarction (MI) or sham surgery. This series includes single-cell transcriptome data from (Ki67-RFP+) cardiac cells collected from neonatal murine hearts, adult homeostatic murine hearts or adult murine hearts collected 14 days following myocardial infarction (MI), ischemic/perfusion (I/R) or sham surgery.
Publication Title
Profiling proliferative cells and their progeny in damaged murine hearts.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 156 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of NSCLC. A prognostic signature of 17 genes showed the best association with post-surgery survival time. The performance of the signatures was validated using a patient cohort of similar size
Publication Title
Gene expression-based classification of non-small cell lung carcinomas and survival prediction.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Therefore, we performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e., good outcome (OS and DFS>50months) versus bad outcome (OS<19months and DFS<7months). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue. The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components, such as ITGB1 and EPHA2, were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with -catenin being also highly upregulated in metastatic tissue. Thus, we conclude that components of the integrin and ephrin pathways and EMT-related genes might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis.
Publication Title
Molecular markers associated with outcome and metastasis in human pancreatic cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples