Project description:Maintenance of proper phenotypic state of mammary epithelial cells is crucial for normal function, however the molecular networks underlying control of various cellular phenotypes are not well understood. To date most studies have assessed the impact of extracellular signals on a single phenotypic response, such as proliferation, or have focused on elucidation of molecular changes associated with single perturbations. However, these approaches ignore that ligands frequently induce multiple phenotypic changes and that similar phenotypic responses can be induced by multiple ligands. As a consequence, little is known about the core molecular mechanisms that drive cells to different phenotypic states. Here we deeply profiled the phenotypic and molecular responses of MCF10A mammary epithelial cells to a diverse panel of ligands known to have a role in the normal mammary gland. These ligands elicited multiple phenotypic responses, including changes in proliferation, migration, and differentiation status. Analysis of companion RNAseq, ATACseq, and proteomic data identified distinct molecular features associated with ligand treatments and phenotypic changes. These data provide a robust resource to address questions about how environmental signals are encoded into molecular and phenotypic responses, the associations between molecular modalities, and temporal encoding of molecular and phenotypic responses.
Project description:Maintenance of proper phenotypic state of mammary epithelial cells is crucial for normal function, however the molecular networks underlying control of various cellular phenotypes are not well understood. To date most studies have assessed the impact of extracellular signals on a single phenotypic response, such as proliferation, or have focused on elucidation of molecular changes associated with single perturbations. However, these approaches ignore that ligands frequently induce multiple phenotypic changes and that similar phenotypic responses can be induced by multiple ligands. As a consequence, little is known about the core molecular mechanisms that drive cells to different phenotypic states. Here we deeply profiled the phenotypic and molecular responses of MCF10A mammary epithelial cells to a diverse panel of ligands known to have a role in the normal mammary gland. These ligands elicited multiple phenotypic responses, including changes in proliferation, migration, and differentiation status. Analysis of companion RNAseq, ATACseq, and proteomic data identified distinct molecular features associated with ligand treatments and phenotypic changes. These data provide a robust resource to address questions about how environmental signals are encoded into molecular and phenotypic responses, the associations between molecular modalities, and temporal encoding of molecular and phenotypic responses.
Project description:Matrisome-focused integrative omics analysis reveals stromal phenotypes associated with consensus molecular subtypes in colorectal cancer
This reseaerch is conducted using colorectal cancer.
TMT 11plex experiment
Project description:Despite remarkable progress made in human genome-wide association studies, there remains a substantial gap between statistical evidence for genetic association and functional comprehension of the underlying mechanisms. To bridge the gap, we perform integrative genomic analysis of blood pressure and related phenotypes in the spontaneously hypertensive rat, an animal model of essential hypertension, searching causal genes and causal pathways. We identify 28 potential target genes, including rat homologs of human transcriptome-wide association study loci, for the tested traits and provide experimental evidence supporting the presence of key disease pathways and core disease-related gene loci in the genetic architecture of hypertension.
Project description:The overall goal of this study is to identify the genomic binding of RUNX1 in MCF10A cells. We used ChIPseq (chromatin immunoprecipitation assay followed by deep sequencing) to identify the binding sites of RUNX1 in MCF10A cells. We performed ChIPseq of RUNX1 using parental MCF10A cells and did not identify high confident binding sites. To overcome this hurdle, we first generated a RUNX1 deleted MCF10A cell line using CRISPR-Cas9. We then transduced this RUNX1 KO MCF10A cells with lentiviruses that inducibly expresses RUNX1. After treating RUNX1 inducible MCF10A cells with 1 ug/ml doxycycline for 24 hours, we performed ChIPseq of RUNX1.
Project description:10 Breast cancer cell lines profiled on the Affymetrix U133 Plus 2.0 platform used in conjunction with matched DNA copy number and DNA methylation data for integrative analysis. In total, 10 samples were used. The MCF10A profile used as normal was obtained from GSM254525 and the remaining 2 cell lines were obtained from caBIG. Full RMA normalized expression profile is attached.