Differential Wnt-mediated Programming and Arrhythmogenesis in Right versus Left Ventricles
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ABSTRACT:
PROVIDER: PRJNA417059 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Differential Wnt-mediated Programming and Arrhythmogenesis in Right versus Left Ventricles [wntgof]
| PRJNA417134 | ENA
Project description:Differential Wnt-mediated Programming and Arrhythmogenesis in Right versus Left Ventricles [wntlof]
| PRJNA417071 | ENA
Project description:Several inherited arrhythmias primarily affect the right ventricle, including Brugada syndrome and arrhythmogenic cardiomyopathy, however the molecular basis of this chamber predilection is not well understood. Right and left ventricular cardiomyocytes derive from distinct progenitor populations. Here, we show that Hrt2, a gene associated with Brugada syndrome, is a direct target of Wnt signaling in the right ventricle and Notch signaling in the left ventricle. Perturbations of Wnt and Notch signaling during development and in the adult lead to chamber-specific transcriptional effects on Hrt2 expression associated with distinct binding patterns to Hrt2 enhancers. Differential enhancer binding is present at early developmental stages when the signaling pathways are active and persists into adulthood. Consistent with chamber-specific regulation, mice deficient in Wnt transcriptional activity dysregulate only a small fraction of transcripts in common between ventricles. Wnt target gen es important for cellular electrophysiology are differentially regulated, resulting in perturbed cardiac conduction and cellular electrophysiological parameters only within the right ventricle. Ex vivo and in vivo physiologic stimulation of the right ventricle is sufficient to induce ventricular tachycardia in Wnt transcriptionally inactive hearts, while left ventricular stimulation has no effect. Taken together, these data delineate mechanisms underlying ventricular-specific arrhythmia susceptibility due to embryonic programming.
2018-12-14 | GSE106507 | GEO
Project description:Several inherited arrhythmias primarily affect the right ventricle, including Brugada syndrome and arrhythmogenic cardiomyopathy, however the molecular basis of this chamber predilection is not well understood. Right and left ventricular cardiomyocytes derive from distinct progenitor populations. Here, we show that Hrt2, a gene associated with Brugada syndrome, is a direct target of Wnt signaling in the right ventricle and Notch signaling in the left ventricle. Perturbations of Wnt and Notch signaling during development and in the adult lead to chamber-specific transcriptional effects on Hrt2 expression associated with distinct binding patterns to Hrt2 enhancers. Differential enhancer binding is present at early developmental stages when the signaling pathways are active and persists into adulthood. Consistent with chamber-specific regulation, mice deficient in Wnt transcriptional activity dysregulate only a small fraction of transcripts in common between ventricles. Wnt target gen es important for cellular electrophysiology are differentially regulated, resulting in perturbed cardiac conduction and cellular electrophysiological parameters only within the right ventricle. Ex vivo and in vivo physiologic stimulation of the right ventricle is sufficient to induce ventricular tachycardia in Wnt transcriptionally inactive hearts, while left ventricular stimulation has no effect. Taken together, these data delineate mechanisms underlying ventricular-specific arrhythmia susceptibility due to embryonic programming.
2018-12-14 | GSE106506 | GEO
Project description:Left and right heart ventricles of adult male mice were profiled to determine the differences in gene expression, control, coordination and signaling fabrics Two-sides (L= left, R = right) gene expression profiling experiment in adult mouse male (M) ventricles (V). 4 biological replicates: MVL1-4, MVR1-4.
2013-03-21 | E-GEOD-45348 | biostudies-arrayexpress
Project description:Left and right heart ventricles of adult male mice were profiled to determine the differences in gene expression, control, coordination and signaling fabrics
2013-03-21 | GSE45348 | GEO
Project description: Not available
| S-EPMC6200419 | biostudies-literature
Project description:Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy left and right cardiac ventricles indicated that left ventricle-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the right ventricle. Single-cell RNA-sequencing (scRNA-seq) analysis of the two populations confirmed that Postn+ CFs are more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed unique expansion of two less-well characterized subpopulations of CFs (Igfbp3+ and Inmt+). These findings demonstrate that LV and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform whether LV and RV fibrosis require distinct treatments.
2024-02-28 | GSE254914 | GEO
Project description:Cardiac mesenchymal stromal cells from right and left ventricles display different biological properties.
| PRJNA596219 | ENA
Project description:Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy left and right cardiac ventricles indicated that left ventricle-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the right ventricle. Single-cell RNA-sequencing (scRNA-seq) analysis of the two populations confirmed that Postn+ CFs are more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed unique expansion of two less-well characterized subpopulations of CFs (Igfbp3+ and Inmt+). These findings demonstrate that LV and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform whether LV and RV fibrosis require distinct treatments.
2024-02-28 | GSE255542 | GEO