Purpose: The goals of this study are to compare transcriptome profiling (RNA-seq) in pancreatic intraepithelial neoplasm (PanIN) cells exposed to tobacco-specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and to examine the upregulated pathways. Overall design: Methods: Total RNA was isolated from PanIN cells treated with tobacco specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for 5 and 50 days. Samples were processed for RNA-seq using standard methods on the Illumina HiSeq 2000 platform. Sequencing was performed in two multiplexed lanes of 100-bp single-end sequencing, which resulted in 75 million mappable reads per lane. The Illumina pipeline was used for base calling and quality filtering of sequence reads. Transcript assembly and abundance estimates of transcripts in fragments per kilobase of exon per million fragments mapped (FPKM) were performed by Cufflinks. Significant differences in total gene and transcript expression, splice site, transcription start site (TSS) and promoter usage were determined using a false discovery rate (FDR)-adjusted P-value. This study provides a framework for understanding transcriptional changes when pancreas cells exposed to tobacco specific nitrosamine.
Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer.
Specimen part, Cell line, Subject, Time
View SamplesIn order to elucidate the developmental origin of oligodendrocyte precursor cells (OPCs) and get a better understanding of the several waves of OPC generation, we look at several timepoints and perform single-cell RNA-seq on Pdgfra positive populations in Mice. Overall design: Mice line used in this study included Pdgfra-cre-ERT/RCE and the Pdgfra-H2BGFP knock-in mouse. Embryos at embryonic day 13.5 and pups from post-natal day 7, from both genders of the Pdgfra-GFP mice line were used to extract OPCs, as well as E12.5 and P3 tamoxifen injected mice harvested at P7. The single cell suspension from embryonic and post-natal tissue was FACS sorted for GFP positive cells using a BD FACSAria III Cell Sorter B5/R3/V3 system.
Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development.
Cell line, Subject
View SamplesFor assessing the cancer-causing potential for humans of a chemical compound, the conventional approach is the use of the 2-year rodent carcinogenicity bioassay, thus alternatives such as in vitro toxicogenomics are highly desired. In the present study, the transcriptomics responses following exposure to genotoxic (GTX) and non-genotoxic (NGTX) hepatocarcinogens and non-carcinogens (NC) in five liver-based in vitro models, namely conventional and epigenetically-stabilized cultures of primary rat hepatocytes, the human hepatoma-derived HepaRG and HepG2 cell lines and the human embryonic stem cell-derived hepatocyte-like cells hES-Heps are examined and compared.
Transcriptomic responses generated by hepatocarcinogens in a battery of liver-based in vitro models.
Specimen part, Cell line, Treatment
View SamplesThe local protein composition of chromatin is important for the regulation of transcription and other functions. By integrative analysis of genome-wide binding maps of 53 broadly selected chromatin components in Drosophila cells, we show that the genome is segmented into five principal chromatin types that are defined by unique, yet overlapping combinations of proteins, and form domains that can extend over >100 kb. We identify a novel repressive chromatin type that covers about half of the genome and lacks classic heterochromatin markers. Furthermore, transcriptionally active euchromatin consists of two distinct types that differ in molecular organization and H3K36 methylation, and regulate distinct classes of genes. Finally, we provide evidence that the different chromatin types act as guides that help to target DNA-binding factors to specific subsets of their recognition motifs. These results uncover basic principles of chromatin organization in a higher eukaryote. For this study, we generated whole-genome DamID binding profiles of 45 chromatin proteins in Drosophila Kc167 cells. Additionally, we perused published binding data of 8 chromatin proteins and generated a binding profile of one exogenous (yeast) DNA binding factor in Kc167 cells. On the same array platform, we obtained ChIP-on-chip profiles of histone H3, H1, H3K9me2, H3K27me3, H3K4me2, and H3K79me3. See supplementary files below. Gene expression was measured by RNA tag profiling. See GeneCounts supplementary file below. Overall design: [1] RNA tag sequences were optained on an Illumina GAII with the digital gene expression (DGE) module from duplicate RNA samples. [2] All DamID and ChIP experiments were done in Drosophila Kc167 cells in duplicate. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing. Every experiment was done in duplicate in the reverse dye orientation, where Dam-fusion material was hybridized over Dam-only material. For ChIP, immunoprecipitated material was hybridized over ChIP input material. 18 previously-submitted Samples were included in this study. 10 of 18 Samples have been renormalized for the GSE22069 study: GSM509087, GSM509088, GSM509089, GSM509090, GSM509091, GSM509092, GSM509093, GSM509094, GSM509095, GSM509096 New GSM accession numbers have been issued for these 10 samples. 8 of 18 Samples are identical in the original studies and in GSE22069: GSM423290, GSM423291, GSM423298, GSM423299, GSM493592, GSM493593, GSM509085, GSM509086 [3] The genomic locations in files GSE22069_norm_aggregated_discretized_tiling_arrays.txt and GSE22069_norm_aggregated_tiling_arrays.txt are relative to FlyBase release 5 (BDGP R5/dm3).
Systematic protein location mapping reveals five principal chromatin types in Drosophila cells.
Cell line, Treatment, Subject
View SamplesAstrocyte-secreted proteins induce synapse formation between isolated retinal ganglion cell (RGC) neurons in culture. We asked whether 2 of these proteins, glypican 4 (Gpc4) or thrombospondin 1 (TSP1) induce synapse formation by regulating gene expression in RGCs.
Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation.
Treatment
View SamplesAims/hypothesis: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it.
Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming.
Specimen part
View SamplesIn several models of obesity-induced diabetes, increased lipid accumulation in the liver has been associated with decreased diabetes susceptibility. For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and C57BLKS mice but, only on the C57BLKS background do the mice develop beta-cell loss leading to severe diabetes while C57BL/6 mice are relatively resistant. Liver triglyceride levels in the resistant C57BL/6 mice are 3 to 4 fold higher than in C57BLKS.
Systems genetics of susceptibility to obesity-induced diabetes in mice.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming capacity of Nanog is functionally conserved in vertebrates and resides in a unique homeodomain.
Specimen part
View SamplesNanog null neural stem (NS) cells were reprogrammed to naive pluripotency in 2i/LIF conditions with mouse (m) Nanog and human (h) Nanog. Global gene expression in resulting iPS cells was compared to embryonic stem (ES) cells and nanog null NS cells.
Reprogramming capacity of Nanog is functionally conserved in vertebrates and resides in a unique homeodomain.
Specimen part
View SamplesNanog null neural stem (NS) cells were reprogrammed to naive pluripotency in 2i/LIF conditions with chick (c) and zebrafish (z) Nanog orthologs. Global gene expression was compared to iPS cells derived with mouse (m) Nanog.
Reprogramming capacity of Nanog is functionally conserved in vertebrates and resides in a unique homeodomain.
Specimen part
View Samples