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Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm [RNA-seq]

ABSTRACT: Genome-wide identification of gene regulatory networks for murine cardiac conduction system (CCS)

ORGANISM(S): Mus musculus

PROVIDER: GSE152065 | GEO | 2022/12/02

REPOSITORIES: GEO

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Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm [ATAC-seq]

Project description:Genome-wide identification of gene regulatory networks for murine cardiac conduction system (CCS)

2022-12-02 | GSE152064 | GEO

Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm.

Project description:Comprehensive cis-regulatory landscapes are essential for accurate enhancer prediction and disease variant mapping. Although cis-regulatory element (CRE) resources exist for most tissues and organs, many rare - yet functionally important - cell types remain overlooked. Despite representing only a small fraction of the heart's cellular biomass, the cardiac conduction system (CCS) unfailingly coordinates every life-sustaining heartbeat. To globally profile the mouse CCS cis-regulatory landscape, we genetically tagged CCS component-specific nuclei for comprehensive assay for transposase-accessible chromatin-sequencing (ATAC-Seq) analysis. Thus, we established a global CCS-enriched CRE database, referred to as CCS-ATAC, as a key resource for studying CCS-wide and component-specific regulatory functions. Using transcription factor (TF) motifs to construct CCS component-specific gene regulatory networks (GRNs), we identified and independently confirmed several specific TF sub-networks. Highlighting the functional importance of CCS-ATAC, we also validated numerous CCS-enriched enhancer elements and suggested gene targets based on CCS single-cell RNA-Seq data. Furthermore, we leveraged CCS-ATAC to improve annotation of existing human variants related to cardiac rhythm and nominated a potential enhancer-target pair that was dysregulated by a specific SNP. Collectively, our results established a CCS-regulatory compendium, identified novel CCS enhancer elements, and illuminated potential functional associations between human genomic variants and CCS component-specific CREs.

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Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm

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

2022-12-02 | GSE152066 | GEO

Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm

Project description:Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm

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Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm [RNA-seq]

Project description:Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm [RNA-seq]

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Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm [ATAC-seq]

Project description:Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm [ATAC-seq]

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Transcriptomic profiling of the postnatal mouse cardiac conduction system

Project description:The cardiac conduction system (CCS) comprises a network of highly specialized cells, including sinoatrial node, atrioventricular node, His bundle, bundle branches and Purkinje fibers. To uncover the transcriptomic landscape across the postnatal CCS and comparative profiling of different CCS components, we conducted scRNA-seq in purified postnatal CCS cells and spatial transcriptomic analysis in the postnatal CCS reporter mouse heart.

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Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution

Project description:The cardiac conduction system (CCS) consists of distinct components including the sinoatrial node (SAN), atrioventricular node (AVN), His bundle, bundle branches (BB) and Purkinje fibers (PF). Despite an essential role for the CCS in heart development and function, the CCS has remained challenging to interrogate due to inherent obstacles including small cell numbers, large cell type heterogeneity, complex anatomy and difficulty in isolation. We used single-cell RNA-sequencing (scRNA-seq) to perform genome-wide analysis of gene expression of the CCS at single-cell resolution.

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The cis-Regulatory Landscape of Cardiac Rhythm

Project description:Genome-wide identification of gene regulatory networks for murine cardiac conduction system

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Efficient Generation of Cardiac Purkinje Fiber-like Cells from ESCs by Activating cAMP Signaling

Project description:Analysis of gene expression of mESC-derived cardiac purkinje fiber-like cells at mRNA level. Dysfunction of the cardiac conduction system (CCS) significantly impacts pathogenesis of arrhythmia, a major cause of morbidity and mortality. Strategies to derive cardiac conduction cells including Purkinje fiber cells (PC) would facilitate models for mechanistic studies and drug discovery, and also provide new cellular materials for regenerative therapies. A high-throughput chemical screen using CCS:lacZ and Contactin2:eGFP (Cntn2:eGFP) reporter embryonic stem cell (ESC) lines was used to discover a small molecule, sodium nitroprusside (SN), that efficiently promotes the generation of cardiac cells that express gene profiles and generate action potentials of PC-like cells. Imaging and mechanistic studies suggest that SN promotes the generation of PC from cardiac progenitors initially expressing cardiac myosin heavy chain, and that it does so by activating cAMP signaling. These findings provide a novel strategy to derive scalable PC, along with insight into the ontogeny of CCS development.

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