Project description:Genome-wide circular RNA profiling analyses in left ventricles (LVs) from cardiac-specific GRK-beta1AR transgenic (TG) and/or miR-150 TG mice treated with isoproterenol (ISO) were performed to identify novel circular RNAs regulated by beta-arrestin-mediated beta1AR signaling and miR-150 in the heart.
2023-01-01 | GSE199290 | GEO
Project description:RNA-Seq of mouse heart tissue: ISO
Project description:Genome-wide transcriptomic analyses in left ventricles (LVs) from cardiac-specific GRK-beta1AR transgenic (TG) and/or miR-150 TG mice treated with isoproterenol (ISO) were performed to identify novel targets of beta-arrestin-mediated beta1AR signaling and miR-150 in the heart.
Project description:Mice were subjected to either isoprenaline (ISO, 30 mg/kg*d) or isoprenaline and phenylephrine (ISO/PE, 30 mg/kg*d each) for a period of 4 days via osmotic minipumps. At that timepoint, both ISO and ISO/PE treated animals showed a similar increase in heart weight to tibia length ratios. ECG-telemetry data collected from other individuals indicate a similar increase heart rate and normal blood pressure after 4 days of both ISO and ISO/PE exposure. Cardiac function was not assessed at that particular timepoint.
2022-02-23 | GSE195466 | GEO
Project description:CLEAR-CLIP of mouse heart tissue: ISO
Project description:Mechanical overload in the heart induces pathological remodeling that typcially leads to heart failure. We sought to build an in vitro model of heart failure by applying cyclic stretch to engineered isotropic (iso) and anisotropic (aniso) NRVM tissues. We used micoarrays to determine the effects of longitudinal and transvserse cyclic stretch on gene expression in engineered NRVM cardiac tissues. We found that cyclic stretch induced up-regulation of several known indicators of heart faliure, independent of the direction of stretch. NRVMs were seeded on silicone membranes coated with isotropic (iso) fibronectin (FN) or micropatterned with FN (aniso), cultured statically for 1h (t=0h), and stretched for increasing amount of time (t=6h, 24h, 96h) before RNA extraction and hybridization on Affymetrix microarrays. For aniso tissues, stretch was applied in either the longitudinal (long) or transverse (trans) direction. RNA was collected over six primary NRVM harvests and thus RNA was also extracted and analyzed from samples seeded for 1h (at t=0h) on iso FN to be used to normalize across cell harvests.
Project description:Covalent Bruton's tyrosine kinase inhibitors (BTKis) have transformed the treatment of B-cell non-Hodgkin lymphoma (B-NHL), including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), but their activity has been limited by off-target toxicity and acquired drug resistance. TG-1701 is a novel irreversible and highly specific BTKi being presently under study in a phase 1 clinical trial in patients with relapsed/refractory B-NHL alone and in combination with ublituximab, a CD20 antibody, and umbralisib, a dual PI3Kδ and CK1ε inhibitor. Here we show, for the first time that phosphoproteomic analysis of CLL patients receiving a BTKi (TG-1701) led to a non-supervised clustering that matched the clinical outcomes and separated a group of “responders” from a group of “non-responders”. This clustering was based on a selected list of 96 phosphosites, with Ikaros-Ser442/445 phosphorylation as a potential marker for TG-1701 efficacy. RNA-seq analysis followed by qPCR and western blot validation further revealed that TG-1701 treatment blunted the Ikaros gene signature only in responder patients, as well as in BTKi-sensitive, but not BTKi-insensitive, B-NHL cell lines and xenografts. Importantly, and in contrast with ibrutinib, TG-1701 did not impair FcγR-driven antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) triggered by the anti-CD20 antibodies rituximab and ublituximab in a multicellular MCL co-culture system. In addition, TG-1701 cooperated with ublituximab coupled to umbralisib (also referred as the U2 regimen) in reducing the tumor growth in both ibrutinib-sensitive and ibrutinib-insensitive mouse models of MCL. Altogether, these data validate phosphoproteomic as a broken thread to omics analysis in the clinic and support the use of TG-1701-U2 combination in R/R B-NHL patients, irrespective of prior response to ibrutinib.
Project description:The goal of this study is to compare the NGS-derived heart transcriptome profiling (RNA-seq) between Tg(hsp70:dn-xBrg1) and wild-type sibling injured hearts.