Transcriptome analysis of embryonic hearts from germline RBPMS knockout mutants
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ABSTRACT:
PROVIDER: PRJNA1214380 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the function of RNA-binding protein with multiple splicing (RBPMS) in heart, we establish a germline RBPMS knockout mutant strain. RNA seq of neonatal (P1) hearts was performed.
2025-05-05 | GSE287749 | GEO
Project description:To investigate the function of RNA-binding protein with multiple splicing (RBPMS) family, RBPMS and RBPMS2, in heart, we establish two RBPMS/2 double knock out mutant strains using cardiomyocyte specific Cre delete strains. Xenopus laevis light chain 2 (XMLC2) promoter CRE mice (Breckenridge et al., 2007) were crossed to RBPMSflox/flox / RBPMS2flox/flox animals to generate the RBPMS/2flox/flox / XMLC2-Cre mice line. In a parallel approach, we crossbred RBPMSflox/flox / RBPMS2flox/flox mice with animals carrying alpha myosin-heavy chain (Myh6) Cre (αMyHC-Cre) (Agah et al., 1997), resulting in the RBPMS/2flox/flox / aMyHC-Cre line. RNA seq of E11.5 (XML-Cre) and E16.5 (αMyHC-Cre) embryonic hearts was performed.
2025-05-05 | GSE234908 | GEO
Project description:To investigate the function of RNA-binding protein with multiple splicing (RBPMS) family, RBPMS and RBPMS2, in heart, we establish two RBPMS/2 double knock out mutant strains using cardiomyocyte specific Cre delete strains. Xenopus laevis light chain 2 (XMLC2) promoter CRE mice (Breckenridge et al., 2007) were crossed to RBPMSflox/flox / RBPMS2flox/flox animals to generate the RBPMS/2flox/flox / XMLC2-Cre mice line. In a parallel approach, we crossbred RBPMSflox/flox / RBPMS2flox/flox mice with animals carrying alpha myosin-heavy chain (Myh6) Cre (αMyHC-Cre) (Agah et al., 1997), resulting in the RBPMS/2flox/flox / aMyHC-Cre line. RNA seq of E11.5 (XML-Cre) and E16.5 (αMyHC-Cre) embryonic hearts was performed.
2025-05-05 | GSE234910 | GEO
Project description:To investigate the role of RBPMS in endothelial cells, endothelial cells were isoldated from 18-month-old mice hearts and treated with lentivirus expressing empty vector or lentivirus overexpressing RBPMS. We then performed gene expression profiling analysis using data obtained from RNA-seq.
2025-04-16 | GSE229919 | GEO
Project description:Dysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and a potential genetic mechanism of cardiomyopathy. Despite epidemiological associations between Parkinson disease and heart failure, the role of Parkin and mitophagic quality control in maintaining normal cardiac homeostasis is poorly understood.We used germline mutants and cardiac-specific RNA interference to interrogate Parkin regulation of cardiomyocyte mitochondria and examine functional crosstalk between mitophagy and mitochondrial dynamics in Drosophila heart tubes. 5 wild-type mouse hearts; 4 germline Parkin knockout mouse hearts Please note that the mouse cardiac examples were an adjunct to the Drosophila studies that comprised most of the associated publication. However, mRNA-sequencing was only performed on the mouse samples, not the Drosophila heart tubes.
2015-10-31 | E-GEOD-74517 | biostudies-arrayexpress
Project description:Background: Modulation of mRNA splicing acts as an important layer of gene regulation, in addition to transcriptional regulation and epigenetic modifications. RNA binding proteins (RBPs) play essential roles in mediating RNA splicing and are key regulators of heart development and function. Our previous studies demonstrated that RBPMS (RNA-binding protein with multiple splicing) regulates cardiac development through modulating mRNA splicing during embryogenesis. Here we explored the postnatal function of RBPMS in the heart. Methods: We ablated Rbpms in the heart by generating a cardiac-specific knockout mouse line (Myh6-Cre, Rbpmsfl/fl), and evaluated its cardiac functions by histology, echocardiography, and gene expression. Paired-end RNA sequencing and RT-PCR were performed to identify and validate splicing targets of RBPMS in adult mouse hearts. Proximity-dependent Biotin Identification (BioID) assay and mass spectrometry analysis were performed to identify RBPMS binding partners. We also measured contractility and calcium fluxes in isolated mouse cardiomyocytes, and contractile forces of cardiac papillary muscle. Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) were also used as a model to explore the influence of RBPMS on contractility of human cardiomyocytes. Results: he absence of Rbpms in the heart led to dilated cardiomyopathy (DCM) and heart failure, causing early death in mice. Mice with cardiac-specific knockout of Rbpms showed myocardium noncompaction with reduced cardiomyocyte number at the neonatal stage and developed DCM with pervasive myocardial fibrosis in adulthood. We found that RBPMS mediates a largely distinct RNA splicing profile in adult mouse hearts compared to neonatal hearts, indicating a stage-specific modulation of alternative RNA splicing by RBPMS. In adult hearts, RBPMS mainly influenced alternative splicing of genes associated with sarcomere structures and cardiomyocyte contraction, such as Ttn, Pdlim5 and Nexn, to generate new protein isoforms. In neonatal hearts, RBPMS influenced the splicing of cytoskeletal genes. RBMPS was associated with spliceosome factors and other RNA binding proteins that play important roles in the heart, such as RBM20 and GATA4. Importantly, we found that the absence of Rbpms caused severe cardiomyocyte contractile defects and reduced calcium sensitivity in both mouse and hiPSC-CMs. Our results demonstrated that Rbpms is crucial for postnatal cardiac function and cardiomyocyte contractility by regulating RNA alternative splicing. Conclusions: Loss of Rbpms in the heart causes reduced cardiomyocyte number and impaired cardiomyocyte contraction, leading to DCM and heart failure.
2023-11-03 | GSE218672 | GEO
Project description:Transcriptome analysis of cardiac specific depletion of RBPMS and RBPMS2 embryonic hearts
| PRJNA983722 | ENA
Project description:Transcriptome analysis of cardiac specific depletion of RBPMS and RBPMS2 embryonic hearts [sch7_rnaseq]
| PRJNA983732 | ENA
Project description:Transcriptome analysis of cardiac specific depletion of RBPMS and RBPMS2 embryonic hearts [sch4_rnaseq]
| PRJNA983729 | ENA
Project description:Differentiated Vascular Smooth Muscle Cells (VSMCs) express a unique network of splice isoforms (smooth muscle specific alternative splicing - SM-AS) in functionally critical genes including those comprising the contractile machinery. We previously described RNA Binding Protein Multiple Splicing (RBPMS) as a potent driver of contractile, aortic tissue like SM-AS in VSMCs using rodent models. What is unknown is how RBPMS affects VSMC phenotype and behaviour. Here, we use human embryonic stem cell-derived VSMCs (hES-VSMCs) to dissect the role of RBPMS in SM-AS in human cells and determine the impact on VSMC phenotypic properties. hES-VSMCs are inherently immature and display only partially differentiated SM-AS patterns while RBPMS levels are undetectable endogenously. Hence, we used an over-expression system and found that RBPMS induces SM-AS patterns in hES-VSMCs akin to the contractile tissue VSMC splicing patterns in multiple events. We present in silico and experimental findings that support RBPMS’ splicing activity as mediated through direct binding and via functional cooperativity with splicing factor RBFOX2 on a significant subset of targets. Finally, we demonstrate that RBPMS can alter the motility and the proliferative properties of hES-VSMCs to mimic a more differentiated state. Overall, this study emphasizes a critical splicing regulatory role for RBPMS in human VSMCs and provides evidence of phenotypic modulation by RBPMS.
2024-12-19 | GSE242826 | GEO