We found that a small molecule inhibitor of PRMT4 inhibited cell growth of a subset of multiple myeloma cell lines. To identify biomarkers that predict the sensitivity of myeloma cells to PRMT4 inhibition, we performed transcriptomic analysis of multiple myeloma cell lines. Overall design: Amplicon sequencing of thirteen multiple myeloma cell lines was performed on the Ion Torrent platform. Steady-state gene expression profile of sensitive cells were compaired with that of insensitive cells.
TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma.
Specimen part, Cell line, Subject
View SamplesDendritic cells (DCs) are pivotal for both recognition of antigens and control of an array of immune responses by recognizing microbes through distinct pattern recognition receptors (PRRs). The first microbial component to be studied in detail and known to cause septic shock is endotoxin (LPS). DCs recognize LPS via Toll-like receptor TLR-47. LPS causes many changes in the DCs, but the elicitation of cytokine production is perhaps the one with clear biologic relevance.
Targeting of microRNA-142-3p in dendritic cells regulates endotoxin-induced mortality.
Specimen part, Treatment
View SamplesPredicting liver injury after exposure to toxic industrial chemicals is complicated by the large number of potential environmental contaminants, mixtures, and exposure dose and route scenarios. Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be fibrogenic by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male Sprague-Dawley rats dosed with varying concentrations of three fibrogenic compounds (allyl alcohol, carbon tetrachloride, and 4,4-methylenedianiline) and two non-fibrogenic compounds (bromobenzene and dexamethasone) were conducted. Fibrosis was definitively diagnosed by histopathology. Transcriptomics data matched the predictions made using the DrugMatrix data with greater than 90% accuracy. Microarray data were verified using a 67-plex panel Bioplex assay, confirming that the 67-plex panel constituted a biomolecular signature of hepatic fibrosis (Figure). Necrosis and inflammatory infiltration were comorbid with fibrosis. Interaction analysis identified 24 genes specific for the fibrosis phenotype. The protein product of the gene most strongly correlated with the fibrosis phenotype (Pcolce) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (p<0.05). PCOLCE is a novel biomarker candidate of fibrotic injury. These results support the development of gene panels for liver injury and may suggest bridging biomarkers for molecular mediators linked to histopathology.
Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis.
Sex, Specimen part
View SamplesWe discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration. Overall design: CRX+ flow sorted cells from human retina derived organoids were collected at 6 time points during differentiation (day (D) 37, 48, 67, 90, 134, 220).
Treatment Paradigms for Retinal and Macular Diseases Using 3-D Retina Cultures Derived From Human Reporter Pluripotent Stem Cell Lines.
Specimen part, Subject
View SamplesMuscle biopsies taken from vastus lateralis muscle of 15 men and 15 women after 3 days of standardized diet and activity to examine effects of sex and age
Sex-related differences in gene expression in human skeletal muscle.
No sample metadata fields
View SamplesRNA from 5 mice with postdevelopmental knockout of myostatin and 5 mice with normal myostatin expression was analyzed with comprehensive oligonucleotide microarrays. Myostatin depletion affected the expression of several hundred genes at nominal P < 0.01, but fewer than a hundred effects were statistically significant according to a more stringent criterion (false discovery rate < 5%). Most of the effects were less than 1.5-fold in magnitude. In contrast to previously-reported effects of constitutive myostatin knockout, postdevelopmental knockout did not downregulate expression of genes encoding slow isoforms of contractile proteins or genes encoding proteins involved in energy metabolism. Several collagen genes were expressed at lower levels in the myostatin-deficient muscles, and this led to reduced tissue collagen levels as reflected by hydroxyproline content. Myostatin knockout tended to down-regulate the expression of sets of genes with promoter motifs for Smad3, Smad4, myogenin, NF-B, serum response factor, and numerous other transcription factors. Main conclusions: in mature muscle, myostatin is a key transcriptional regulator of collagen genes, but not genes encoding contractile proteins or genes encoding proteins involved in energy metabolism.
Skeletal muscle gene expression after myostatin knockout in mature mice.
Sex, Age, Specimen part
View SamplesMuscle biopsies taken from vastus lateralis muscle of 30 normal subjects and 19 FSHD subjects (see PubMed ID 17151338)
Expression profile of FSHD supports a link between retinal vasculopathy and muscular dystrophy.
No sample metadata fields
View SamplesThe gene expression pathways leading to muscle pathology in facioscapulohumeral dystrophy (FSHD) remain to be elucidated. This muscular dystrophy is caused by a contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35.2. We compared expression of control and FSHD myoblasts and myotubes (three preparations each) on exon microarrays (Affymetrix Human Exon 1.0 ST) and validated FSHD-specific differences for representative genes by qRT-PCR on additional myoblast cell strains. The FSHD and control myoblasts used for these experiments were shown to grow and differentiate into myotubes equally efficiently as control myoblasts. There were no significant FSHD-control differences in RNA levels for MYOD1 and MYOG at the myoblast and myotube stages and for MYF5 and MYF6 at the myoblast stage. In contrast, 295 other genes were dysregulated at least 2-fold in FSHD vs. control myoblasts (p <0.01, adjusted for multiple comparisons).
Gene expression during normal and FSHD myogenesis.
Specimen part
View SamplesWe evaluated the transcriptome changes induced by infection of Hela 229 cells with Shigella flexneri. The sample set consists of a control (mock), total population of infected sample and infected sample sorted into Shigella positive and Shigella negative population. Overall design: Transcriptmic profiles of HeLa cells infected with Shigella were generated by high throughput sequencing using Illumina HiSeq2000.
Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia.
No sample metadata fields
View SamplesTo have a global picture of the targets of the mir-29b-2-5p, we assessed transcriptome changes, by deep-sequencing, of HeLa cells transfected with this miRNA or a control miRNA (cel-miR-231). Overall design: Transcriptmic profiles of HeLa cells treated miR-29b-2-5p and control-miR were generated by deep sequencing, using Illumina HiSeq2000.
Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia.
No sample metadata fields
View Samples