Analysis of human iPS-derived cardiomyocytes exposed to glucose, endothelin-1 and cortisol in vitro. Treatment produces a surrogate diabetic cardiomyopathic phenotype. Results provide insight into the pathways regulated by the treatment in the cardiomyocyte.
Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.
Specimen part, Treatment, Time
View Samplesdrl expression initiates during gastrulation and condenses as a band of cells at the prospective lateral embryo margin. In late epiboly, drl:EGFP is detectable as a band of scattered EGFP-fluorescent cells; after gastrulation, drl:EGFP-positive cells coalesce at the embryo margin that then in somitogenesis break down into the anterior and posterior lateral plate with subsequent cell migrations that form the posterior vascular/hematopoietic stripes and the anterior cardiovascular and myeloid precursors.
Chamber identity programs drive early functional partitioning of the heart.
Age, Specimen part
View SamplesWe tested the gene expression difference between PDGFRa+ fibroblasts FACS sorted from nulliparous balb/c mouse mammary glands and 6 days post-weaning mammary glands Overall design: 2 biological replicates of fibroblasts from nulliparous mammary glands and 3 biological replicates of fibroblasts from 6 days post-weaning mammary glands were used for comparison.
Physiologically activated mammary fibroblasts promote postpartum mammary cancer.
Specimen part, Cell line, Subject
View SamplesWe report the application of ultrashort metabolic labeling of RNA for high-throughput profiling of RNA processing in Drosophila S2 cells. Overall design: Examination of 3 different labeling timepoints in Drosophila S2 cells.
The kinetics of pre-mRNA splicing in the <i>Drosophila</i> genome and the influence of gene architecture.
Cell line, Subject
View SamplesPolyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD.
Sex, Specimen part, Time
View SamplesAlas2 gene encodes the rate-limiting enzyme in heme biosynthesis. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis-elements strongly reduced GATA-1-induced Alas2 transcription, heme biosynthesis, and GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing Alas2 function in Alas2 cis-element-mutant (double mutant) cells by providing its catalytic product 5-aminolevulinic acid (5-ALA) rescued heme biosynthesis and the GATA-1-dependent genetic network. We discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. Overall design: G1E-ER-GATA-1 WT and double mutant cells were examined. Untreated WT, beta-estradiol-treated WT, beta-estradiol-treated double-mutant, and beta-estradiol/5-ALA-treated double-mutant cells were subjected to RNA-seq.
Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.
Treatment, Subject
View SamplesUsing Affymetrix microarray technology we analyzed the gene expression profiles of the most important pathological categories of bladder cancer in order to detect potential marker genes. Applying an unsupervised cluster algorithm we observed clear differences between tumor and control samples, as well as between superficial and muscle invasive tumors. According to cluster results, the T1 high grade tumor type presented a global genetic profile which could not be distinguished from invasive cases. We described a new measure to classify differentially expressed genes and we compared it against the B-rank statistic as a standard method. According to this new classification method, the biological functions overrepresented in top differentially expressed genes when comparing tumor versus control samples were associated with growth, differentiation, immune system response, communication, cellular matrix and enzyme regulation. Comparing superficial versus invasive samples, the most important overrepresented biological category was growth and, specifically, DNA synthesis and mitotic cytoskeleton. On the other hand, some under expressed genes have been clearly related to muscular tissue contamination in control samples. Finally, we demonstrated that a pool strategy could be a good option to detect the best differentially expressed genes between two compared conditions.
DNA microarray expression profiling of bladder cancer allows identification of noninvasive diagnostic markers.
No sample metadata fields
View SamplesTransient over-expression of defined combinations of master regulator genes can effectively induce cellular reprogramming: the acquisition of an alternative predicted phenotype from a differentiated cell lineage. This can be of particular importance in cardiac regenerative medicine wherein the heart lacks the capacity to heal itself, but simultaneously contains a large pool of fibroblasts. In this study we determined the cardio-inducing capacity of ten transcription factors to actuate cellular reprogramming of mouse embryonic fibroblasts into cardiomyocyte-like cells. Over-expression of transcription factors MYOCD and SRF alone or in conjunction with Mesp1 and SMARCD3 significantly enhanced the basal but necessary cardio-inducing effect of the previously reported GATA4, TBX5, and MEF2C. In particular, combinations of five or seven transcription factors significantly enhanced the activation of cardiac reporter vectors, and induced an upregulation of cardiac-specific genes. Global gene expression analysis also demonstrated a significantly greater cardio-inducing effect when the transcription factors MYOCD and SRF were used. Detection of cross-striated cells was highly dependent on the cell culture conditions and was enhanced by the addition of valproic acid and JAK inhibitor. Although we detected Ca2+ transient oscillations in the reprogrammed cells, we did not detect significant changes in resting membrane potential or spontaneously contracting cells. This study further elucidates the cardio-inducing effect of the transcriptional networks involved in cardiac cellular reprogramming, contributing to the ongoing rational design of a robust protocol required for cardiac regenerative therapies.
Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming.
Specimen part
View SamplesInrauterine growth restriction was induced by chronic hyper insulinemia in pregnant rats and differential gene expression was studied using affymetrix rat genome RAE230A.Data was analysed using SAM.
Adult hypertension in intrauterine growth-restricted offspring of hyperinsulinemic rats: evidence of subtle renal damage.
No sample metadata fields
View SamplesSplenocytes from lymphoreplete, unmanipulated mice were analyzed for basal mRNA levels. We hypothesized, based on previous data from our lab and others, that many cytokine/inflammatory response genes would show an increase from na誰ve CD5lo<CD5hi<Virtual memory. Overall design: mRNA was analyzed from mouse splenocytes separated into na誰ve CD5lo, na誰ve CD5hi, and virtual memory cells. Mice were lymphoreplete and unmanipulated.
Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner.
Cell line, Subject
View Samples