biostudies-arrayexpressMetabolomicsUnknownTranscriptomicsGenomicsProteomicsStefan MeinkeIllumina NovaSeq XRNA-seq of coding RNAMus musculusMus musculushttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-14882We report the heart RNA-sequencing of control animals (C57BL/6N genetic background, wild type) and animals of a mouse model of cardiometabolic heart failure (HFpEF) treated or not with RBM20 antisense oligonucleotide. HFpEF was induced using a 2-hit regimen, in which male mice were fed with a high-fat diet (D12492, Research Diet Inc) and L-NAME 0.5g/L (nitric oxide synthase inhibitor) in drinking water, beginning at 3 months of age and continue for 22 weeks. Control male mice were fed with a control diet (D12450K, Research Diet Inc) and water without L-NAME This study aims to investigate the therapeutic effect of antisense oligonucleotide (ASO)-mediated downregulation of the cardiac splice factor RBM20 in HFpEF-like conditions. Adult mice were subcutaneously injected with 25 mg/kg/week for 6 weeks. RNA from left ventricular tissue was isolated using TRIzol followed by a clean-up with the QIAGEN RNA micro kit, cDNA libraries were generated using the Illumina TruSeq Stranded mRNA Sample Prep Kit 2x150 single-end sequenced on Illumina NovaSeq X Plus. The RNA-Sequencing analysis confirms that RBM20 ASO treatment increased the expression of compliant titin isoforms and improved diastolic function, even in the context of cardiometabolic stress.biostudies-arrayexpressSample Collection - After 8 month the animals were killed by cervical dislocation and the hearts were removed, frozen in liquid nitrogen and stored at -80°C for further processing. The heart tissue was ground to a powder with mortar and pestle under liquid nitrogen.Nucleic Acid Extraction - RNA from 4 left ventricles per group were isolated using TRIzol (Thermo Fisher), treated with DNAseI (Qiagen) followed by a clean-up with the Qiagen RNA micro kit.Library Construction - The cDNA libraries were generated using the TruSeq Stranded mRNA Sample Prep Kit (Illumina). Both RNA integrity and cDNA library size distribution were confirmed with TapeStation (Agilent Technologies). Concentration of indexed libraries was determined using Qubit High-Sensitivity DNA kit (Invitrogen).Sequencing - Libraries were pooled to a final concentration of 10 nM and were sequenced on an Illumina NovaSeq X Plus (single-end 150 bp).Sample Treatment - We used the 2-hit regimen20, in which mice were fed with a high-fat diet (D12492, Research Diet Inc) and L-NAME 0.5g/L (nitric oxide synthase inhibitor) in drinking water, beginning at 3 months of age and continue for 16 weeks. Control mice were fed with a control diet (D12450K, Research Diet Inc) and water without L-NAME. After 16 weeks on the 2-hit regimen, when the mice had fully developed the HFpEF-like phenotype, 2hit mice and control mice were randomly received Rbm20-ASOs or PBS treatment. Rbm20-ASOs were administered through subcutaneous injections at 25 mg/kg, once a week for 6 weeks. Following this treatment period (6 weeks of ASO/PBS treatment, or 22 weeks in a 2-hit regimen), these mice were employed in endpoint studiesOrganizationMINSEQE ScoreAssays and DataMAGE-TAB FilesMichael GotthardtStefan MeinkefalseHeart RNA-seq of control mice and a mouse model of cardiometabolic heart failure (HFpEF) treated with Rbm20 antisense oligonucleotidesWe report the heart RNA-sequencing of control animals (C57BL/6N genetic background, wild type) and animals of a mouse model of cardiometabolic heart failure (HFpEF) treated or not with RBM20 antisense oligonucleotide. HFpEF was induced using a 2-hit regimen, in which male mice were fed with a high-fat diet (D12492, Research Diet Inc) and L-NAME 0.5g/L (nitric oxide synthase inhibitor) in drinking water, beginning at 3 months of age and continue for 22 weeks. Control male mice were fed with a control diet (D12450K, Research Diet Inc) and water without L-NAME This study aims to investigate the therapeutic effect of antisense oligonucleotide (ASO)-mediated downregulation of the cardiac splice factor RBM20 in HFpEF-like conditions. Adult mice were subcutaneously injected with 25 mg/kg/week for 6 weeks. RNA from left ventricular tissue was isolated using TRIzol followed by a clean-up with the QIAGEN RNA micro kit, cDNA libraries were generated using the Illumina TruSeq Stranded mRNA Sample Prep Kit 2x150 single-end sequenced on Illumina NovaSeq X Plus. The RNA-Sequencing analysis confirms that RBM20 ASO treatment increased the expression of compliant titin isoforms and improved diastolic function, even in the context of cardiometabolic stress.2026-03-19T00:00:00Z2026-03-19T02:03:21.327Z2025-02-28T12:12:37.969ZE-MTAB-14882ERP169754EFO_0002944EFO_0004170EFO_0005518EFO_0003738EFO_0004184EFO_0003969