Project description:This dataset comprises L1000 and image-based cell-morphology profiles for small-molecule perturbations. Profiles were measured for ~18,000 compounds derived from diversity-oriented synthesis activities at the Broad Institute Center for the Science of Therapeutics, ~10,000 compounds selected from the Molecular Libraries Small-Molecule Repository (MLSMR), and ~2,000 known bioactive compounds. Each of the three subsets was selected to be structurally diverse. MLSMR compounds were further selected to have diverse biological performance. Imaging profiles were measured for a total of ~30,000 compounds. We used a "cell-painting" assay to stain seven major cellular components with fluorescent dyes followed by automatic image capture and analysis to extract shape, texture, and intensity parameters. The imaging assay protocol has been published by Gustafsdottir SM et al. L1000 profiles were measured for ~20,000 compounds. All experiments were performed with U-2 OS cells. Among other activities, we have analyzed these data using cheminformatics approaches to derive structure-based associations with patterns of performance in the profiles. The generation of this dataset was supported by the Molecular Libraries Program of the National Institutes of Health (U54-HG005032). Data made available as part of this project includes L1000 data and image-based cell-morphology profiles for small-molecule perturbations. Please follow the steps here to download the data: https://www.pnas.org/content/111/30/10911
Project description:Uterine leiomyosarcoma (ULMS) is a poorly understood gynecologic cancer with few effective treatments. This study explores molecular events involved in ULMS with the goal of identifying strategies. Genome-wide transcriptional profiling were used to compare clinically well-annotated specimens of myometrium, leiomyoma and leiomyosarcoma.
Project description:Regulation of gene expression is linked to the organization of the genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in the gene expression profile. However, little is known about the changes on the level of transcriptional regulation. Here, we used a multi-omics approach and integrated ATAC-, RNA- and NET-seq to identify age-related changes in the chromatin landscape of murine liver and to investigate how these are linked to transcriptional regulation. We provide the first systematic inventory of the connection between aging, chromatin accessibility and transcriptional regulation in a whole tissue. Aging in murine liver is characterized by an increase in chromatin accessibility at promoter regions, but not in an increase of transcriptional output. Instead, aging is accompanied by a decrease of promoter-proximal pausing of RNA polymerase II (Pol II). We propose that these changes in transcriptional regulation are due to a reduced stability of the pausing complex and may represent a mechanism to compensate for the age-related increase in chromatin accessibility in order to prevent aberrant transcription.
Project description:Epithelial-stromal interactions in the uterus are required for normal uterine functions such as pregnancy, and multiple signaling pathways are essential for this process. Although Dicer and microRNAs (miRNA) have been implicated in several reproductive processes, the specific role of Dicer and miRNA in uterine development is not known. To address the roles of miRNA in the regulation of these key uterine pathways, we generated a conditional knockout (cKO) of Dicer in the postnatal uterine epithelium and stroma using progesterone receptor (PR)-Cre. These Dicer cKO are sterile with small uteri, which demonstrate significant defects including absence of glandular epithelium and enhanced stromal apoptosis, beginning at postnatal day 15 with expression of Cre and deletion of Dicer. Although these mice had normal serum steroid hormone levels, critical uterine signaling pathways, including progesterone-responsive genes, Indian hedgehog signaling, and the Wnt/Beta-catenin canonical pathway, were dysregulated at the mRNA level. Gene expression profiling data from pools of Dicer cKO and control uteri groups, at 15 days. two group comparison
Project description:Transcriptional profiles of cultured human cancer cell lines treated with small molecules: Expression of 978 representative genes is measured in 39 cell lines perturbed by 13 thousands of small molecules.
Project description:Transcriptional profiles of multiple cells treated with small molecule perturbagens: The expression level is measured for 978 representative genes in 15 cell lines treated with 241 small molecules.
Project description:Transcriptional profiles of multiple cell and perturbation types: cells are treated with chemical perturbagens and CRISPR reagents. The expression level for 978 representative genes is measured.
Project description:Transcriptional profiles of cultured human breast cancer cell lines treated with small molecules: 5 cell lines are treated with 109 small molecules and the expression of 978 representative genes is measured, as a part of the LINCS Joint Project.
Project description:Transcriptional profiles of multiple cell and perturbation types: cells are treated with chemical and genetic perturbations. The expression level for 978 representative genes is measured.
Project description:Transcriptional profiles of multiple cell and perturbation types: 23 cells are treated with 311 chemical perturbagens and CRISPR reagents. The expression level for 978 representative genes is measured.
