Project description:Transcriptome analysis to map transcriptomes of Mps1DK p53null-driven aneuploid T-ALL, to determine correlation between copy number changes and expression changes and to map the transcriptional response to CIN Transcriptomes of T-ALL samples described in the accompanying manuscript were compared to the transcriptomes of thymocytes of 6-weeks old wild type mice
Project description:Mps1DK and p53 loss were combined in T-cells specificely leading to early onset and highly aggressive aneuploid T-ALL. Tumors were characterized for (recurrrent) copy number changes with a focus on whole chromosome abnormalities. DNA content was compared to the DNA content of sex-matched uninfiltrated control liver samples from litter mates 27 Mps1DK p53f/f of Mps1DK p53f/+ tumors and 5 p53 f/f control tumors
Project description:Analysis of the transcriptional response to aneuploidy in mouse epidermis. In this study we measured the transcriptional response to aneuploidy by aboragting the spindle checkpoint in mouse epidermis. We found that, whereas spindle checkpoint inactivation in the epidermis is tolerated, but results in metabolic deranged cells, SAC abrogation kills bulge stem cells Mad2; K14-Cre mice were sacrificed at indicated timepoints and epidermis was separated from dermis using overnight trypsin. RNA was isolated and expression patterns were compared between K14-Cre; Mad2f/f and Cfre negative animals for all timepoints.
Project description:Identify gene expression patterns of different neural precursor cells derived from human embryonic stem cells. The total of 12 samples were analyzed which could be grouped into 4 groups
Project description:We used a plamsid-based assay to identify novel S. cerevisiae mutants with abnormal Break Induced Replication (BIR) efficiencies. We pooled the ca. 5000 yeast deletion mutants from the systematic deletion library and compared the relative tranformation efficiencies of a circular versus linear truncated minichromosome using tag arrays. Our main result is the identification of Fun30 as a novel chromatin remodelr facilitating DNA end resection. A pool of ca. 5000 yeast deletion mutants from the systematic deletion library was transformed with a circular minichromosome on one hand, and with a linear truncated minichromosome on the other hand. Transformants were recovered, DNA was extracted and the systematic tags were PCR amplified with complementary dyes for the two transformations. Amplified tags were mixed and hybridized on a tag array. The overall experiment was done twice.
Project description:Single cell RNA sequencing was performed to allow expression-based identification of tumor versus normal cells from glioblastoma patient specimens. Identified tumor cells were then analyzed to assess the expression tumor-cell specific expression of TRIM26, WWP2, and SOX2.
Project description:There is a growing realization that some aging-associated phenotypes/diseases have an epigenetic basis. Here we report the first genome-scale study of epigenomic dynamics during normal human aging. We identify aging-associated differentially methylated regions (aDMRs) in whole blood in a discovery cohort, and then replicate these aDMRs in sorted CD4+ T-cells and CD14+ monocytes in an independent cohort, suggesting that aDMRs occur in precursor haematopoietic cells. Further replication of the aDMRs in buccal cells, representing a tissue that originates from a different germ-layer compared with blood, demonstrates that the aDMR signature is a multi-tissue phenomenon. Moreover, we demonstrate that aging-associated DNA hypermethylation occurs predominantly at bivalent chromatin domain promoters. This same category of promoters, associated with key developmental genes, is frequently hypermethylated in cancers and in vitro cell culture, pointing to a novel mechanistic link between aberrant hypermethylation in cancer, aging, and cell culture. We measured the methylation state of 27,578 CpG sites (Illumina HumanMethylation27 array) in whole blood samples from 93 heathy human females aged between 49 and 74, to discover sites which change methylation state with age.
Project description:Analysis of the Saccharomyces cerevisiae transcriptome in the absence of the chromatin remodeler Fun30 A wild type and a fun30 null strain were grown in rich medium. Each culture was divided in two before RNA extraction. Two hybridizations were performed, both using independent RNA preparations from WT and the fun30 null mutant.
Project description:This SuperSeries is composed of the following subset Series: GSE16581: Genomic landscape of meningiomas: gene expression GSE16583: Genomic landscape of meningiomas: genotyping Refer to individual Series
Project description:Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed global genetic and genomic analysis of 85 meningioma samples of various grades. Copy number alterations were assessed by 100K SNP arrays and correlated with gene expression, proliferation indices, and clinical outcome. In addition to chromosome 22q loss, which was detected in the majority of clinical samples, chromosome 18q and 6q loss significantly predicted recurrence and was associated with anaplastic histology. Five classes of meningiomas were detected by gene expression analysis that correlated with copy number alterations, recurrence risk, and malignant histology. These classes more accurately predicted tumor recurrence than Ki-67 index, the gold standard for determining risk of recurrence, and highlight substantial expression heterogeneity between meningiomas. These data offer the most complete description of the genomic landscape of meningiomas and provide a set of tools that could be used to more accurately stratify meningioma patients into prognostic risk groups. Tumor biopsies from 43 female and 25 male subjects with sporadic meningioma were identified from the UCLA Neuro-oncology Program Tissue Bank through institutional review board approved protocols. 43 tumors were designated "benign" WHO I, 19 tumors were "atypical" WHO II, and 6 were "anaplastic" WHO III. Gene expression analysis was performed on the 68 tumor biopsies.