biostudies-arrayexpressSyed Murtuza BakerMus musculushttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-14646Radiotherapy (RT)-induced cardiac toxicity (RICT) is widely acknowledged as a major side effect of RT, which encompasses cardiovascular complications. Despite advances in understanding the underlying biological mechanisms, a complete characterisation of the molecular changes induced by RT in the different cardiac regions is still absent. Here, a multi-omics approach was adopted to longitudinally characterise the unique response to radiation in the heart base (including ventricular base and right atrium), or the apex of the heart. The ventricular base showed a cardiomyopathy phenotype, with pronounced molecular perturbations in metabolism and electrical conduction, while changes in tissue structure were predominant in ventricular apex. We then identified a molecular signature showing that base radiation-mediated remodelling leads to a higher incidence of atrial fibrillation (AF). This study represents a comprehensive characterisation of differential spatiotemporal radiation effects in the heart and highlights several biological pathways that are potentially clinically actionable for cardiac radioprotection and monitoring.biostudies-arrayexpressSample Treatment - Female C57BL/6J aged 12 weeks (16-20gr; Envigo, UK) were housed in standard housing conditions for laboratory animals (12-hour light-dark cycle, controlled temperature of 19–22°C and humidity of 40–65%) and provided with a standard diet and water ad libitum.Animals were anaesthetised with 2% isoflurane and were irradiated with X-rays (220 kV,13mA) at a dose rate of 2.67 Gy/min on a small-animal radiation research platform (SARRP; Xstrahl Life Sciences, UK). Briefly, cone beam CT (60kV, 0.7mA) collected 360 projections over 1 minute and it was used to reconstruct the 3D image of the whole mouse to identify the heart. Muriplan software was adopted to contour the region of interest, either the base or the apex of the heart to deliver the radiation. A total dose of 16Gy was delivered to the specific substructure of the heart using a 3 × 9 mm collimator.Library Construction - Used 10X sample collection protocol, CG000409-10x GenomicsSample Collection - Ten weeks post RT, one control mouse, one irradiated at the base and one at the apex were killed by a regulated procedure. Hearts were immediately extracted, washed in Phosphate buffered saline (PBS) and processed to be embedded in wax.According to 10x protocol for Visium, 5 micrometer sections were collected.Nucleic Acid Extraction - Used 10X sample collection protocol, detailed in CG000409-10x Genomics userguideSequencing - Used Illumina Novaseq6000 protocol, detailed in novaseq6000 user documentOrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesData Transformation - We used spaceranger 2.0 to process the data. The images and the json files are attached for the processingUnknownTranscriptomicsGenomicsProteomicsIllumina NovaSeq 6000RNA-seq of coding RNA from single cellsMus musculusSyed Murtuza BakerKaye WilliamsfalseUnveiling the distinctive impact of radiation on cardiac ventricular regions and the right atrium using multi-omics approachesRadiotherapy (RT)-induced cardiac toxicity (RICT) is widely acknowledged as a major side effect of RT, which encompasses cardiovascular complications. Despite advances in understanding the underlying biological mechanisms, a complete characterisation of the molecular changes induced by RT in the different cardiac regions is still absent. Here, a multi-omics approach was adopted to longitudinally characterise the unique response to radiation in the heart base (including ventricular base and right atrium), or the apex of the heart. The ventricular base showed a cardiomyopathy phenotype, with pronounced molecular perturbations in metabolism and electrical conduction, while changes in tissue structure were predominant in ventricular apex. We then identified a molecular signature showing that base radiation-mediated remodelling leads to a higher incidence of atrial fibrillation (AF). This study represents a comprehensive characterisation of differential spatiotemporal radiation effects in the heart and highlights several biological pathways that are potentially clinically actionable for cardiac radioprotection and monitoring.2025-11-20T00:00:00Z2025-11-20T02:02:23.467Z2024-11-28T17:24:39.222ZE-MTAB-14646ERP166633EFO_0002944EFO_0004170EFO_0005684EFO_0005518EFO_0003816EFO_0004184EFO_0003969