Wild-type and the acs2Ts1 mutant yeasts were shifted from 25deg to 37deg. After 60 minutes, Yeasts were harvested and divided into 2 x 2 cell samples. Total RNAs were purified from 4 populations.
Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription.
No sample metadata fields
View SamplesRegulatory T cells (Treg) are common in the tumor microenvironment in both human pancreatic cancer and in genetically engineered mouse models of the disease. Previous studies in orthotopic syngeneic models of pancreatic cancer -recapitulated in our own data- indicated that Treg depletion results CD8+ T cell-mediated tumor regression. In human patients and in mouse models, regulatory T cells accumulate during the onset of Pancreatic Intraepithelial Neoplasia (PanIN), the earliest steps of carcinogenesis. We thus generated a genetic model to investigate the role of regulatory T cells during the onset of pancreatic carcinogenesis. Unexpectedly, depletion of Tregs during early stages of carcinogenesis led to accelerated tumor progression. Overall design: We are using KC;Foxp3DTR mice generated by crossing KC (Ptf1a-Cre;LSL-KrasG12D) with Foxp3DTR (B6.129(Cg)-Foxp3tm3(DTR/GFP)Ayr/J, Jackson Laboratory). We depleted Foxp3-expressing Tregs by Diphtheria Toxin (DT) injection to determine the requirement of Tregs during oncogenic Kras induced Pancreatic Intraepithelial Neoplasia (PanIN) formation and maintenance. To investigate the mechanisms underlying the tumor-promoting effect of Treg depletion in KC; Foxp3DTR mice we performed RNA sequencing (RNAseq) for myeloid cells (DAPI-EpCAM-CD45+CD11b+) flow-sorted from KC and KC; Foxp3DTR pancreata.
Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis.
Subject
View SamplesRat mammary glands were obtained from individual rats in RXR treated (a) and control (b) conditions (12 rats in each condition). The 24 samples were hybridized individually. Also, in each condition, samples were combined into different pools of 2, pools of 3, pools of 12. Technical replicates were also run.
On the utility of pooling biological samples in microarray experiments.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Gene Expression Barcode: leveraging public data repositories to begin cataloging the human and murine transcriptomes.
Treatment
View SamplesWe used yeast RNA to estimate background binding for each probe on the human U133 plus 2.0 array.
The Gene Expression Barcode: leveraging public data repositories to begin cataloging the human and murine transcriptomes.
Treatment
View SamplesWe hybridized yeast RNA to the mouse 430 2.0 array to estimate the background binding for each probe.
The Gene Expression Barcode: leveraging public data repositories to begin cataloging the human and murine transcriptomes.
Treatment
View SamplesDespite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the TXG-MAP). Accounting for the overall transcriptional activity resulting from treatment, we explain mechanisms of toxicity and predict distinct toxicity phenotypes using module associations. We demonstrate that early network responses compliment traditional histology-based assessment in predicting outcomes for longer studies and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum stress and Nrf2 activation. Module-based molecular subtypes of cholestatic injury derived using rat translate to human. Moreover, compared to gene-level analysis alone, combining module and gene-level analysis performed in sequence identifies significantly more phenotype-gene associations, including established and novel biomarkers of liver injury.
Toxicogenomic module associations with pathogenesis: a network-based approach to understanding drug toxicity.
Sex, Specimen part
View SamplesPre-LVAD and explanted ischemic and nonischemic cardiomyopathy and nonfailing hearts all normalized with RMA
Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin.
Sex, Age, Specimen part
View SamplesGene expression profiling of epidermal samples obtained from sun-exposed and sun-protected body sites from younger (<35 years old) and older (>60 years old) individuals. The Affymetrix U133A plus 2.0 array was used to obtain gene expression data. Samples included 4 younger sun exposed epidermal samples, 4 older sun exposed epidermal samples, 3 younger sun protected epidermal samples, 5 older sun protected epidermal samples.
Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin.
Sex, Age, Specimen part
View Samples