Epithelial-mesenchymal transition (EMT) has been linked to cancer progression and metastatic propensity. The 4T1 tumor is a clinically relevant model of spontaneous breast cancer metastasis. Here we characterize 4T1-derived cell lines for EMT, in vitro invasiveness and in vivo metastatic ability. Contrary to expectations, the 67NR cells, which form primary tumors but fail to metastasize, express vimentin and N-cadherin, but not E-cadherin. 4T1 cells, however, express E-cadherin, are highly migratory and invasive, and metastasize to multiple sites. The 66cl4 metastatic cells display mixed epithelial and mesenchymal markers, but are less migratory and invasive than 67NR cells. These findings demonstrate that the metastatic ability of breast cancer cells does not correlate with genotypic and phenotypic properties of EMT per se, and suggest that other processes may govern metastatic capability. Gene expression analysis also has not identified differences in EMT markers, but has identified several candidate genes that may influence metastatic ability.
Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis.
Sex, Specimen part
View SamplesWe report transcriptomes of pre-sorted skin wound dermal cells. Post-wounding day (PWD) 12, 15 and 21 Zombie-neg;tdTomatoHi cells were FACS sorted from Sm22-Cre;TdTomato mice. Overall design: Examination of single cell heteregeneity in large skin wounds on PWD 12, 15 and 21
Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds.
Specimen part, Cell line, Treatment, Subject
View SamplesWe are investigating the transcriptional response of yeast to treatment with enediynes or gamma radiation, which generate different extents of double or single strand breaks in DNA.
The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA.
No sample metadata fields
View SamplesWe report transcriptomes of myofibroblasts from mouse skin wounds. Myofibroblasts were FACS sorted as Zombie-neg;tdTomato-hi cells from Sm22-Cre;TdTomato mice. We identified and analyzed 4,120 differentially expressed transcripts across four post-wounding time points, day 12, day 15, day 21 and day 26. Overall design: Examination of FACS sorted wound myofibroblasts from four consecutive post-wounding time points
Regeneration of fat cells from myofibroblasts during wound healing.
Specimen part, Subject
View SamplesN6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (“m6A levels”), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3’ untranslated regions (3’-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications. Overall design: m6A-LAIC-seq of H1-ESC and GM12878 cell lines, each cell line has two replicates
m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome.
No sample metadata fields
View SamplesPublication Title: DNA methylation alters transcriptional rates of differentially expressed genes and contributes to pathophysiology in mice fed a high fat diet. It is now well established that an intrauterine environment altered by overnutrition or malnutrition can change gene expression patterns through epigenetic mechanisms that may persist through generations. However, it is less clear if overnutrition alters epigenetic control of gene expression in adults, or if whether such mechanisms contribute to the pathology of obesity. Here we test the hypothesis that exposure to a high fat diet alters hepatic DNA methylation and gene expression patterns, and explore the contribution of such changes to the pathophysiology of overnutrition. RNA-seq and targeted high-throughput bisulfite DNA sequencing were used to undertake a systematic analysis of the hepatic response to a high fat diet. A subset of genes was found whose expression levels were altered in concert with DNA methylation changes. Using chromatin immunoprecipitation of RNA polymerase, we determined that hypermethylation correlated with decreased transcription of two of the genes, Phlda1 and Onecut1. A subnetwork of these genes and their nearest neighbors was generated from an existing Bayesian gene network that contained numerous hepatic regulatory genes involved in lipid and body weight homeostasis. Hepatic-specific depletion of Phlda1 in mice decreased the genes in the subnetwork, and led to increased oil droplet size in standard chow-fed mice, an early indicator of steatosis, validating the contribution of this gene to the phenotype. Overall design: 14 mice fed either a high fat/high sucrose (n=7) or low fat/low sucrose (n=7) diet.
DNA methylation alters transcriptional rates of differentially expressed genes and contributes to pathophysiology in mice fed a high fat diet.
Specimen part, Subject
View SamplesSingle-cell sorted cells from the osteocytic cell line Ocy454 were screened for high- and low-Sost/sclerostin expression to see changes in other gene expressions related to Sost/sclerostin.
Carbonic anhydrase III protects osteocytes from oxidative stress.
No sample metadata fields
View SamplesWe report the transcriptional changes in Drosophila after administration of Actin or buffer control Overall design: Examination of transcriptional responses to actin versus buffer injected flies at 3,6 and 24 hours post injection (each time point includes triplicate samples)
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in <i>Drosophila melanogaster</i>.
Sex, Specimen part, Cell line, Subject
View SamplesHere we determine the map of RNA methylation (m6A) in mouse embrionic stem cells, and Mettl3 knock out cells Overall design: Examination of m6A modification sites on the transcriptome of mouse Embryonic stem cells and Embryonic Mettl3 knock out cells, using a m6A specific antibody.
m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNA methylation profiling reveals a predominant immune component in breast cancers.
Specimen part, Disease stage, Cell line, Treatment
View Samples