The onset and progression of breast cancer are linked to genetic and epigenetic changes that alter the normal programming of cells. Epigenetic modifications of DNA and histones contribute to chromatin structure that results in the activation or repression of gene expression. Several epigenetic pathways have been shown to be highly deregulated in cancer cells. Targeting specific histone modifications represents a viable strategy to prevent oncogenic transformation, tumor growth or metastasis. Methylation of histone H3 lysine 4 has been extensively studied and shown to mark genes for expression; however this residue can also be acetylated and the specific function of this alteration is less well known. To define the relative roles of histone H3 methylation (H3K4me3) and acetylation (H3K4ac) in breast cancer, we determined genomic regions enriched for both marks in normal-like (MCF10A), transformed (MCF7) and metastatic (MDA-MB-231) cells using a genome-wide ChIP-Seq approach. Our data revealed a genome-wide gain of H3K4ac associated with both early and late breast cancer cell phenotypes, while gain of H3K4me3 was predominantly associated with late stage cancer cells. Enrichment of H3K4ac was overrepresented at promoters of genes associated with cancer-related phenotypic traits, such as estrogen response and epithelial-to-mesenchymal transition pathways. Our findings highlight an important role for H3K4ac in predicting epigenetic changes associated with early stages of transformation. In addition, our data provide a valuable resource for understanding epigenetic signatures that correlate with known breast cancer-associated oncogenic pathways. Overall design: RNA-Seq of cell lines MCF10A, MCF7 and MDA-MB-231.
Histone H3 lysine 4 acetylation and methylation dynamics define breast cancer subtypes.
No sample metadata fields
View SamplesCharacterization of differential gene expression due to cisplatin resistance in human ovarian cancer spheroids by microarray analysis.
Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.
Specimen part, Cell line
View SamplesThe goals of this study are to study the regulatory network of the two maize endosperm-specific transcription factors O2 and PBF by 16-DAP endosperm transcriptome profiling (RNA-seq) of their mutants and wild type. The results utilize the expression pattern of global genes regulated by PBF and O2 to elucidate their control for storage compounds synthesis in maize kernels. Overall design: The 16-DAP endosperm transcriptome of wild type (WT) and mutants including opaque2, PbfRNAi and PbfRNAi;o2 were generated by RNA-seq with three biological replicates per genotype on Illumina HiSeqTM2500.
Maize endosperm-specific transcription factors O2 and PBF network the regulation of protein and starch synthesis.
Specimen part, Subject
View SamplesThese RNA-seq data were generated to correlate with genomic interaction data in a related Hi-C analysis. MCF10A is a normal-like mammary epithelial cell line and MCF7 is a transformed estrogen responsive breast cancer cell line derived from a metastatic site; both are commonly used in models of breast cancer progression. Analysis revealed a set of genes related to repression of WNT signalling that were both up-regulated in MCF7 and located in genomic regions that had transitioned from closed to open structure in MCF7. Overall design: RNA-seq of MCF10A and MCF7 cells. 3 replicates each. Sequencing was strand-specific and conducted on ribo-depleted RNA.
Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells.
No sample metadata fields
View SamplesAcute lymphoblastic leukemia (ALL) is an heterogeneous disease comprising several subentities that differ for both immunophenotypic and molecular characteristics. Over the years, the biologic understanding of this neoplasm has largely increased. Gene expression profiling has recently allowed to identify specific signatures for the different ALL subsets and permitted identification of pathways deregulated by a given lesion. MicroRNAs (miRNAs) are small non-coding RNAs which play a pivotal role in several cellular functions. In this study, we investigated miRNA and gene expression profiles in a series of adult ALL cases by microarray analysis and combined them by bioinformatic analysis. Interestingly, those miRNAs which are differentially expressed between the ALL classes accounted for a large proportion of miRNA/mRNA expression pairs identified by the above analysis. Moreover, the analysis highlighted several putative miRNA targets involved in apoptosis and cell-cycle regulation.
Characterization of B- and T-lineage acute lymphoblastic leukemia by integrated analysis of MicroRNA and mRNA expression profiles.
Sex, Age, Specimen part
View SamplesUsing the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice autoimmune indications. However, our current knowledge of the role of BTK in immune competence has been gathered in the context of genetic inactivation of btk in both mice and man. Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice. We implicate BTK in tonic BCR signaling, demonstrate dependence of the T3 B cell subset and IgM surface expression on BTK activity, and find that B1 cells survive and function independently of BTK. While BTK inhibition does not impact humoral memory survival, antigen-driven clonal expansion of memory B cells and antibody secreting cell generation are inhibited. These data define the role of BTK in the mature immune system and mechanistically predict the clinical phenotype of BTK inhibition.
Modeling the clinical phenotype of BTK inhibition in the mature murine immune system.
Specimen part
View SamplesClinical Significance: Understanding the differences in colorectal cancer (CRC) aggressiveness and clinical outcomes in relation to tumor stage and different molecular subsets is at most important for designing treatment regimens. However, molecular signatures for specific phenotypic subsets that predict the aggressiveness and clinical outcomes of CRC, specifically in advanced disease stage are lacking. Therefore, for the first time, the current study has identified a set of molecular markers that are associated with aggressive Stage III CRCs that exhibited microsatellite stable and mutant p53 phenotypic features. These findings might aid in designing aggressive treatment regimens and help to provide insights into the development of novel therapeutic targets.
Prognostic significance and gene expression profiles of p53 mutations in microsatellite-stable stage III colorectal adenocarcinomas.
Specimen part, Disease, Disease stage
View SamplesMesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibers through the modulation of the junctional adhesion molecule-A. We conclude that PW1/Peg3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/Peg3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.
PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence.
Sex, Specimen part
View SamplesCell body and pseudopod RNA are differentially regulated during the migration of the metastatic cancer cells.We wanted to identify the RNA which are upregulated in the pseudopodial (PS) fraction as compared to cell body fraction (CB).
Pseudopodial actin dynamics control epithelial-mesenchymal transition in metastatic cancer cells.
Cell line
View SamplesChanges in gene regulation have long been known to play important roles in both innate and adaptive immune responses. However, post-transcriptional mechanisms involved in mRNA processing have been poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Overall design: Transcriptomic profiles of 198 infected (Listeria and Salmonella) and non-infected samples at multiple time points.
Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans.
No sample metadata fields
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