Purpose: Majority of pancreatic cancer (PDAC) patient deaths are associated to the metastatic progression of disease. To identify novel targeted-therapies, a complete understanding of transformation in genetic landscape in tumors during disease progression is needed. Widely in use, the artificially immortalized PDAC cell lines do not rightly represent the progression because of multiple donors and disparate genetic characteristics. To identify key genes underlying the progression of PDAC from localized disease to a metastatic form, we performed whole transcriptome RNA-Sequencing analysis of cell models representing localised to metaststic stage through paired-end deep sequencing Method: Mouse expressing a Cre-activated KrasG12D allele inserted into the endogenous Kras locus, and these mice were crossed with mice expressing Cre recombinase in pancreatic tissue by virtue of a PDX-1 promoter-driven transgene. Next a cross between K-rasG12D Pdx-Cre and p16-/- mice, transgenic K-rasG12D Pdx-Cre p16-/- mice were generated harboring tissue specific mutant Kras and p16 deletion resulting in an earlier appearance of PanIN lesions followed by rapid progression into highly invasive and metastatic pancreatic cancers. Results: Transgenic K-rasG12D Pdx-Cre p16-/- mice developed spontaneous- localized, invasive and metastatic pancreatic tumors and transcriptome of these cell models representing localized, invasive and metastatic pancreatic tumors were sequenced. Conclusions: Based on genetic analysis of a same-lineage genetic background cell models, this study identifies a novel molecular pathway underlying the progression of pancreatic cancer disease. This study shows that Intestine Specific Homeobox (ISX) gene is a novel biomarker unique to pancreatic cancer progression. Overall design: By using tumors from K-rasG12D/p16-/- transgenic mice, we generated a spectrum of spontaneous (without immortalization) murine cell models representing localized (HI-Panc-L), invaise (HI-Panc-I) and metastatic (HI-Panc-M) stages. HI-Panc progression model is a valuable tool and by studying gene expression during progression of pancaretic cancer from localised to metaststic stage in a genetically same linaege wll be beneificail for pancartic cancer reaserch.
Characterization of Novel Murine and Human PDAC Cell Models: Identifying the Role of Intestine Specific Homeobox Gene ISX in Hypoxia and Disease Progression.
Specimen part, Subject
View SamplesReprogramming somatic cells to induced pluripotency by Yamanaka factors is usually slow and inefficient, and is thought to be a stochastic process. We identified a privileged somatic cell state, from which acquisition of pluripotency could occur in a non-stochastic manner. Subsets of murine hematopoietic progenitors are privileged, whose progeny cells predominantly adopt the pluripotent fate with activation of endogenous Oct4 locus after 4-5 divisions in reprogramming conditions. Privileged cells display an ultrafast cell cycle of ~8 hours. In fibroblasts, a subpopulation cycling at a similar ultrafast speed is observed after 6 days of factor expression, and is increased by p53-knockdown. This ultrafast-cycling population accounts for >99% of the bulk reprogramming activity in wildtype or p53-knockdown fibroblasts. We compared the transcriptomes of the fast cycling cells with those of slower hematopoietic progenitors, bulk fibroblasts and established iPS cells. Overall design: 3-5 replicates for each of the six cell types were included: 4 replicates for established iPS cells, 4 replicates for bulk mouse embryonic fibroblasts (MEF), 4 replicates for fast cycling MEF, 4 replicates for slow cycling MEF, 5 replicates for fast cycling granulocyte monocyte progenitors (GMP) and 3 replicates for slow cycling GMP.
Nonstochastic reprogramming from a privileged somatic cell state.
No sample metadata fields
View SamplesGene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy.
TWIST-1 is overexpressed in neoplastic choroid plexus epithelial cells and promotes proliferation and invasion.
Sex, Age
View SamplesGene expression profiling of FACS sorted GFP+ve cells from sexed gonads of transgenic pSF1-eGFP mice
Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic profiling of CHEK2*1100delC-mutated breast carcinomas.
Specimen part
View SamplesBackground: Preterm birth is the leading cause of all infant mortality. In 2004, 12.5% of all births were preterm. In order to understand preterm labor, we must first understand normal labor. Since many of the myometrial changes that occur during pregnancy are similar in mice and humans and mouse gestation is short, we have studied the uterine genes that change in the mouse during pregnancy. Here, we used microarray analysis to identify uterine genes in the gravid mouse that are differentially regulated in the cyclooxygenase-1 knockout mouse model of delayed parturition.
Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse.
No sample metadata fields
View SamplesTaMYB13 is a transcription factor that has been associated with fructan accumulation in previous studies in wheat (Xue et al. 2011 Plant journal 68: 857 - 870). In this study we aimed to find genes regulated by TaMYB13, through overexpression of this transcription factor in wheat and perform expression analysis by making use of Affymetrix genechip assays.
TaMYB13-1, a R2R3 MYB transcription factor, regulates the fructan synthetic pathway and contributes to enhanced fructan accumulation in bread wheat.
Specimen part
View SamplesThe number of transcripts where allelic bias is dependent parent-of-origin was predicted at 100-200 until two recent studies applied RNA-Seq to brain regions from reciprocally crossed inbred mouse strains and identified over a thousand novel imprinted loci, including hundreds present in only males or females. Reanalysis revealed that the vast majority of these novel loci are explained by technical and biological variation of the approach, and are not genuine cases of general or sex-specific parent-of-origin allelic expression. Independent replication projects that, at most, a few dozen novel imprinted transcripts are present in the dataset, in line with previous projections of 100-200 total imprinted transcripts. Overall design: Whole brain transcriptome analysis of E17.5 F1 embryos from reciprocally crossed C57BL/6J and CastEi/J parents
Critical evaluation of imprinted gene expression by RNA-Seq: a new perspective.
No sample metadata fields
View SamplesPyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
Specimen part, Treatment, Time
View SamplesAmplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease. A critical event initiating gene amplification is a DNA double strand break (DSB), which is immediately followed by the formation of a large DNA palindrome. Large DNA palindromes are frequent and non-randomly distributed in the genomes of cancer cells and facilitate further increase in copy number. Although the importance of the formation of large DNA palindromes as a very early event in gene amplification is widely recognized, it is not known 1) how a DSB is resolved to form a large DNA palindrome; and 2) whether any local DNA structure determines the location of large DNA palindromes. We show here that intra-strand annealing following a DNA double-strand break leads to the formation of large DNA palindromes and that DNA inverted repeats in the genome determines the efficiency of this event. Furthermore, in human Colo320DM cancer cells, a DNA inverted repeat in the genome marks the border between amplified and non-amplified DNA. Therefore, an early step of gene amplification is a regulated process that is facilitated by DNA inverted repeats in the genome.
Intrastrand annealing leads to the formation of a large DNA palindrome and determines the boundaries of genomic amplification in human cancer.
No sample metadata fields
View Samples