Using RNA-Seq, we reported novel findings in the comparison of transcriptome profiles of isogenic HMDM and IPSDM during differentiation and polarization. First, IPSDM lost expression of pluripotency markers, had remarkably distinct gene expression profiles relative to precursor iPSCs, and had largely similar gene expression as HMDM. Second, macrophage polarization to M1 was associated with a dramatic change in the transcriptome; expression profiles of IPSDM- and HMDM-derived M1 lines were highly correlated with each other but much less so with their respective IPSDM and HMDM precursors. Third, M2-HMDM lines had limited difference in gene expression compared to their non-polarized precursors, likely due to the known M2-like phenotype of M-CSF differentiated macrophages and their similarity to the IL-4 derived M2 phenotype Finally, through RNA-Seq we identified many new genes modulated during polarization in both HMDM and IPSDM thus providing novel, and potentially regulatory, candidates that warrant further study. Overall design: iPS, IPSDM (including M1/M2) and HMDM (including M1/M2)cells were sequenced by Illumina HiSeq 2000 with poly-A selection
Functional analysis and transcriptomic profiling of iPSC-derived macrophages and their application in modeling Mendelian disease.
No sample metadata fields
View SamplesExpression data from treatment of actinomycin D (2.5uM) and triptolide (500 nM) on MCF7 cells for 2, 4 and 6 hours.
Chemical genomics identifies small-molecule MCL1 repressors and BCL-xL as a predictor of MCL1 dependency.
Cell line, Compound, Time
View SamplesMultiple myeloma (MM) is a currently incurable malignancy of antibody-secreting plasma cells. Long non-coding RNAs (lncRNAs) have been recognised as an important class of regulatory molecules which are increasingly implicated in tumorigenesis. While recent studies have demonstrated changes in expression of lncRNAs in MM, the functional significance and molecular pathways downstream of these changes remain poorly characterised. In this study we have performed CRISPR-mediated deletion of the locus encoding the lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE), a known oncogenic lncRNA that is overexpressed in plasma cells of MM patients and is a marker of poor prognosis. We found that CRISPR-mediated deletion of the CRNDE locus in MM cells decreases proliferation and adhesion properties, increases sensitivity to Dexamethasone and reduces tumour growth in an in vivo xenograft model. Transcriptomic profiling in CRNDE-deleted MM cells demonstrated that CRNDE activates expression of a number of genes previously implicated in the aetiology of MM, including IL6R. We further demonstrate that deletion of the CRNDE locus diminishes IL6 signalling and proliferative responses in MM cells. Altogether this study reveals the IL6 signalling pathway as a novel mechanism by which CRNDE impacts upon MM cell growth and disease progression.
The long non-coding RNA CRNDE regulates growth of multiple myeloma cells via an effect on IL6 signalling.
Cell line
View SamplesThe rates of obesity and sedentary lifestyle are on a dramatic incline, with associated detrimental health effects among women in particular. Although exercise prescriptions are useful for overcoming these problems, success can be hampered by differential responsiveness among individuals in cardiovascular fitness indices (i.e., improvements in strength, lipids, VO2max). Genetic factors appear to play an important role in determining this inter-individual variation in responsiveness. We performed microarray analyses on mRNA in whole blood from 60 sedentary women from a multi-ethnic cohort who underwent 12 weeks of exercise, to identify gene subsets that were differentially expressed between individuals who experienced the greatest and least improvements in fitness based upon a composite fitness score index. We identified 43 transcripts in 39 unique genes (FDR<10%; FC>1.5) whose expression increased the most in high versus low premenopausal female responders. Several (TIGD7, UQCRH, PSMA6, WDR12, TFB2M, USP15) have reported associations with fitness-related phenotypes. Bioinformatic analysis of the 39 genes identified 4 miRNAs whose expression has been linked to cardiovascular diseases (ANKRD22: miR-637, LRRFIP1: miR-132, PRKAR2B: miR-92a, RSAD2:miR-192). These 39 genes were enriched in 6 biological pathways, including the oxidative phosphorylation pathway (p=8.08 x 10-3). Two genes, LRRFIP1 and SNORD30, were also identified with lower expression in high responding postmenopausal women. In summary, we identified gene signatures based on mRNA analysis that define responsiveness to exercise in a largely minority-based female cohort. Importantly, this study validates several genes/pathways previously associated with exercise responsiveness and extends these findings with additional novel genes.
Genomic signatures of a global fitness index in a multi-ethnic cohort of women.
Sex, Race, Time
View SamplesParkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. We study changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls (Discovery set) by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. By applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays, gene expression profiling discriminates patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts were validated by RT-qPCR in an independent cohort of 12 patients and controls (Validation set). Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.
Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients.
Specimen part, Disease
View SamplesThe goal of this study is to investigate if interferon signaling regulates immune checkpoint blockade in mouse melanoma model. Overall design: Transcription profiling for B16, B16 after chronic interferon treatment, B16 derived checkpoint blockade resistant strain 499 and various knockout from 499, coupled with ATA-seq data.
Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade.
Specimen part, Treatment, Subject
View SamplesColon gene expression in human IBD. The three major clinical subsets of Inflammatory Bowel Disease (IBD) include colon-only Crohn's Disease (CD), ileo-colonic CD, and Ulcerative Colitis (UC). These experiments tested differential colon gene expression in these three types of IBD, relative to healthy control samples, and the local degree of mucosal inflammation as measured by the CD Histological Index of Severity (CDHIS). Colon biopsy samples were obtained from IBD patients at diagnosis and during therapy, and healthy controls. The global pattern of gene expression was determined using GeneSpring software, with a focus upon candidate genes identified in a recent genome wide association study in pediatric onset IBD. Data suggested that two of these candidate genes are up regulated in pediatric IBD, partially influenced by local mucosal inflammation.
Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
No sample metadata fields
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