We used microarrays to detail genome-wide gene expression underlying cardiac myocyte pathologies and identified candidate genes and specific pathways affecting cardiac myopathies
Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation.
No sample metadata fields
View SamplesWe apply RNA-seq to limited populations of Innate Lymphoid Cells type 2 and type 3 (ILC2s and ILC3s, respectively) in human individuals infected with acute HIV in the FRESH study. We measured the whole transcriptome of ILC2s and ILC3s in both untreated (n=2) and ART treated (n=2) individuals over the course of infection, in order to compare these populations at key points during infection, namely: viral detection, peak viremia, and weeks past peak viremia (6-7 weeks post detection). Lacking true biological replicates, HIV- patients in the same study (n=9) were used as replicates to conduct Differential Expression (DE) analysis between time points in both ILC2s and ILC3s on a patient by patient basis. In untreated patients, ILC2s and ILC3s differentially expressed genes associated with apoptosis and cell death between peak viremia and viral detection, while ART treated patients' ILC2s and ILC3s demonstrated a mitigated response. Comparing 6-7 weeks after detection with peak viremia revealed a relative decrease in genes associated in cell death in untreated patients, while ART treated patients showed varied responses where several DE genes were associated with immune response. Overall design: RNA-seq of two Innate Lymphoid Cell populations in 2 HIV+ untreated patients, 2 HIV+ ART treated patients, and 9 HIV- patients (control, replicates).
Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.
No sample metadata fields
View SamplesThe goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Subject
View SamplesOver-expression of the Myc transcription factor causes its widespread interaction with regulatory domains in the genome, but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following Myc activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing and mathematical modeling. Transcriptional activation correlated with the highest increases in Myc binding at promoters. Repression followed a reciprocal scenario, with the lowest gains in Myc binding. Altogether, the relative abundance (henceforth, “share”) of Myc at promoters was the strongest predictor of transcriptional responses in diverse cell types, predominating over Myc's association with the co-repressor Miz1. Myc activation elicited immediate loading of RNAPII at activated promoters, followed by increases in pause-release5, while repressed promoters showed opposite effects. Gains and losses in RNAPII loading were proportional to the changes in the Myc share, suggesting that repression by Myc may be largely indirect, owing - at least in part - to competition for limiting amounts of RNAPII. Secondary to the changes in RNAPII loading, the dynamics of elongation and pre-mRNA processing were also rapidly altered at Myc regulated genes, leading to the transient accumulation of partially or aberrantly processed mRNAs. Altogether, our results shed light on how over-expressed Myc alters the various phases of the RNAPII cycle and the resulting transcriptional response. Overall design: Time course profiling of 4sU-labeled and total RNA upon Myc activation in 3T9-MycER mouse fibroblasts
Integrative analysis of RNA polymerase II and transcriptional dynamics upon MYC activation.
Specimen part, Subject
View SamplesRole for naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that, despite pulmonary inflammation, lung-specific CD8+ T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8+ T cells in the inflamed lung and lung-draining lymph nodes down-regulated the expression of effector molecules, those located in the spleen appeared to be partly antigen-experienced and displayed a memory-like phenotype. Since ex vivo-reisolated self-reactive CD8+ T cells were very well capable to respond to the antigen in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8+ T cells in the lung.
CD4+CD25+Foxp3+ regulatory T cells are dispensable for controlling CD8+ T cell-mediated lung inflammation.
Specimen part
View SamplesWe performed genome-wide expression profiling of cells infected with control or RPS14 shRNAs.
Identification of RPS14 as a 5q- syndrome gene by RNA interference screen.
No sample metadata fields
View SamplesWe used an inducible ShRNA system and microarrays to detail the global programme of gene expression underlying neuroblastoma differentiation upon CHAF1A silencing .
Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma.
No sample metadata fields
View SamplesComparison of normal neuroblasts with malignant neuroblastomas (low- and high-stage)
Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesIn order to better understand chondrodysplasia disease mechanisms, we induced hypertrophic chondrocytes from chondrodysplasia-specific iPSCs and analyzed their gene expression profile.
Differentiation of Hypertrophic Chondrocytes from Human iPSCs for the In Vitro Modeling of Chondrodysplasias.
Specimen part
View SamplesJoMa1 cells are pluripotent precursor cells, derived from the neural crest of mice transgenic for tamoxifen-inducible c-Myc. Following transfection with a cDNA encoding for MYCN, cells become immortlized even in the absence of tamoxifen.
MYCN and ALKF1174L are sufficient to drive neuroblastoma development from neural crest progenitor cells.
Specimen part, Cell line
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