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Ventricular T-box 5 in the adult heart ensures normal cardiac conduction and protects from pathologic cardiac remodeling

ABSTRACT: Ventricular T-box 5 in the adult heart ensures normal cardiac conduction and protects from pathologic cardiac remodeling

PROVIDER: PRJNA394989 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5839510.fastq.gz	Fastqsanger.gz
	SRR5839511.fastq.gz	Fastqsanger.gz
	SRR5839512.fastq.gz	Fastqsanger.gz
	SRR5839513.fastq.gz	Fastqsanger.gz
	SRR5839514.fastq.gz	Fastqsanger.gz

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Ventricular T-box 5 in the adult heart ensures normal cardiac conduction and protects from pathologic cardiac remodeling [ChIP-seq]

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.

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Ventricular T-box 5 in the adult heart ensures normal cardiac conduction and protects from pathologic cardiac remodeling [RNA-seq]

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Ventricular T-box 5 in the adult heart ensures normal cardiac conduction and protects from pathologic cardiac remodeling

Project description:This SuperSeries is composed of the SubSeries listed below.

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Expression profiling of the E10.5 cardiac conduction system using MinKGFP BAC transgenic mice

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.

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