Similar Datasets
Project description:Genome-wide identification of gene regulatory networks for murine cardiac conduction system (CCS)
2022-12-02 | GSE152065 | GEO
Project description:Genome-wide identification of gene regulatory networks for murine cardiac conduction system (CCS)
2022-12-02 | GSE152064 | GEO
Project description:Here we define key single-cell transcriptional alterations within cardiac non-myocytes, from ventricles of spontaneously type-2 diabetic (db/db) and control (db/h) mouse hearts ([B6.BKS(D)-Lepr<db>/J], stock #000697). The cell preparation sequenced consisted of metabolically active, live and nucleated non-myocyte cells, which were depleted of endothelial cells. The objective of this experiment was to develop a framework for understanding the dynamics of cardiac cell networks in murine type-2 diabetes, as a resource for future mechanistic studies.
2022-11-29 | E-MTAB-11940 | biostudies-arrayexpress
Project description:Proper development of the specialized cardiac conduction system is crucial for function of the mature heart. Tools for isolation and in-vivo study of the conduction system are limited. The goal of this study was to identify pathways important for conduction system development. We generated a BAC transgenic mouse line, minKGFP, that marks the conduction system during embryogenesis and in adulthood. GFP is expressed in this line at high levels in conduction system myocardium (minkGFP high) and low levels in chamber myocardium (minKGFP low). We used this mouse line to isolate E10.5 conduction system cells, and performed transcriptional profiling on these cells to identify pathways with potential roles in specification of the developing cardiac conduction system.
2015-08-19 | GSE36136 | GEO
Project description:Prolonged electrocardiographic indices reflecting myocardial impulse conduction and repolarization are risk factors for sudden cardiac death and drug-induced arrhythmia. The PR-interval, QRS-duration and QT-interval are heritable traits influenced by multiple genetic and environmental factors. The genetic underpinnings of these traits are still largely unknown. In this study, we leveraged the variability in cardiac gene expression and the variation in PR-, QRS- and QT-intervals among F2 mice harboring the cardiac sodium ion-channel mutation Scn5a-1798insD/+ derived from the 129P2-Scn5a1798insD/+ and FVB/NJ-Scn5a1798insD/+ cross, to isolate novel genes and biological pathways impacting on cardiac conduction and repolarization. Cardiac left-ventricle total RNA from 120 F2-(129P2xFVBN/J)-Scn5a-1798insD/+ mice at 12 to 14 weeks old.
2012-12-01 | E-GEOD-27236 | biostudies-arrayexpress
Project description:Conduction slowing of the electric impulse that drives the heartbeat may evoke lethal cardiac arrhythmias. Mutations in SCN5A, which encodes the pore-forming cardiac sodium channel alpha subunit, are associated with familial arrhythmia syndromes based on conduction slowing. However, disease severity among mutation carriers is highly variable. We hypothesized that genetic modifiers underlie the variability in conduction slowing and disease severity. With the aim of identifying such modifiers, we studied the Scn5a(1798insD/+) mutation in 2 distinct mouse strains, FVB/N and 129P2. In 129P2 mice, the mutation resulted in more severe conduction slowing particularly in the right ventricle (RV) compared to FVB/N. Pan-genomic mRNA expression profiling in the 2 mouse strains uncovered a drastic reduction in mRNA encoding the sodium channel auxiliary subunit beta4 (Scn4b) in 129P2 mice compared to FVB/N. This corresponded to low to undetectable beta4 protein levels in 129P2 ventricular tissue, whereas abundant beta4 protein was detected in FVB/N. Sodium current measurements in isolated myocytes from the 2 mouse strains indicated that sodium channel activation in myocytes from 129P2 mice occurred at more positive potentials compared to FVB/N. Using computer simulations, this difference in activation kinetics was predicted to explain the observed differences in conduction disease severity between the 2 strains. In conclusion, genetically determined differences in sodium current characteristics on the myocyte level modulate disease severity in cardiac sodium channelopathies. In particular, the sodium channel subunit beta4 (SCN4B) may constitute a potential genetic modifier of conduction and cardiac sodium channel disease.
2010-01-12 | GSE19741 | GEO
Project description:Prolonged electrocardiographic indices reflecting myocardial impulse conduction and repolarization are risk factors for sudden cardiac death and drug-induced arrhythmia. The PR-interval, QRS-duration and QT-interval are heritable traits influenced by multiple genetic and environmental factors. The genetic underpinnings of these traits are still largely unknown. In this study, we leveraged the variability in cardiac gene expression and the variation in PR-, QRS- and QT-intervals among F2 mice harboring the cardiac sodium ion-channel mutation Scn5a-1798insD/+ derived from the 129P2-Scn5a1798insD/+ and FVB/NJ-Scn5a1798insD/+ cross, to isolate novel genes and biological pathways impacting on cardiac conduction and repolarization.
2012-12-01 | GSE27236 | GEO
Project description:The retina is composed of ~50 cell-types with specific functions for the process of vision. Identification of the cis-regulatory elements active in retinal cell-types is key to elucidate the networks controlling this diversity. Here, we combined transcriptome and epigenome profiling to map the regulatory landscape of four cell-types isolated from mouse retinas including rod and cone photoreceptors as well as rare inter-neuron populations such as horizontal and starburst amacrine cells. Integration of this information reveals sequence determinants and candidate transcription factors for controlling cellular specialization. Additionally, we refined parallel reporter assays to enable studying the transcriptional activity of large collection of sequences in individual cell-types isolated from a tissue. We provide proof of concept for this approach and its scalability by characterizing the transcriptional capacity of several hundred putative regulatory sequences within individual retinal cell-types. This generates a catalogue of cis-regulatory regions active in retinal cell types and we further demonstrate their utility as potential resource for cellular tagging and manipulation.
2017-10-25 | GSE84589 | GEO
Project description:Sudden cardiac death is the number one cause of death worldwide. Major causes of sudden cardiac death include myocardial infarction and cardiomyopathies. To develop novel therapeutic strategies, we need to identify key factors that are required for proper cardiac function and are dysregulated in the diseased heart. Under this notion, we found T-box 5 (TBX5), a transcription factor regarded solely in the context of congenital heart disease, to be downregulated in human diseased left ventricles. To investigate the effects of TBX5 loss in the adult heart, we generated an inducible ventricular cardiomyocyte specific knock-out mouse model (vTbx5KO). We performed integrative genome-wide chromatin occupancy and transcriptomic analysis and identified 47 downregulated transcripts in vTbx5KO that contain TBX5 active enhancers. The TBX5 targets in the ventricle included genes implicated in cardiac conduction and contraction (Gja1, Kcnj5, Kcng2, Cacna1g, Chrm2), cytoskeleton organization (Fstl4, Pdlim4, Emilin2, Cmya5) as well as cardiac protection upon stress (Fhl2, Gpr22, Fgf16). In line with this analysis, vTbx5KO mice presented cardiac conduction defects and arrhythmias at baseline as well as exacerbated cardiac remodeling upon Angiotensin II-induced hypertrophy. In conclusion, this study uncovers a novel protective role of TBX5 upon cardiac remodeling and renders TBX5 as an interesting therapeutic target.
2020-07-19 | GSE101614 | GEO
Project description:Sudden cardiac death is the number one cause of death worldwide. Major causes of sudden cardiac death include myocardial infarction and cardiomyopathies. To develop novel therapeutic strategies, we need to identify key factors that are required for proper cardiac function and are dysregulated in the diseased heart. Under this notion, we found T-box 5 (TBX5), a transcription factor regarded solely in the context of congenital heart disease, to be downregulated in human diseased left ventricles. To investigate the effects of TBX5 loss in the adult heart, we generated an inducible ventricular cardiomyocyte specific knock-out mouse model (vTbx5KO). We performed integrative genome-wide chromatin occupancy and transcriptomic analysis and identified 47 downregulated transcripts in vTbx5KO that contain TBX5 active enhancers. The TBX5 targets in the ventricle included genes implicated in cardiac conduction and contraction (Gja1, Kcnj5, Kcng2, Cacna1g, Chrm2), cytoskeleton organization (Fstl4, Pdlim4, Emilin2, Cmya5) as well as cardiac protection upon stress (Fhl2, Gpr22, Fgf16). In line with this analysis, vTbx5KO mice presented cardiac conduction defects and arrhythmias at baseline as well as exacerbated cardiac remodeling upon Angiotensin II-induced hypertrophy. In conclusion, this study uncovers a novel protective role of TBX5 upon cardiac remodeling and renders TBX5 as an interesting therapeutic target.
2020-07-19 | GSE101613 | GEO