Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE68025 | GEO | 2016/04/20

SECONDARY ACCESSION(S): PRJNA281593

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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.

2024-06-25 | GSE231547 | GEO

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.

2019-08-01 | GSE132658 | GEO

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

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

2022-12-02 | GSE152065 | GEO

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

A Novel Cre Transgenic Mouse to Label Cardiac Purkinje Fibersduring Ischemic Injury

Project description:Purkinje fibers form a network of specializedventricularmyocardial cells to assure a coordinatedpropagation of the electrical impulseduring normalforheartefficientcontractionof the heart.Thedevelopmental origins of Purkinje fibers and their roles during cardiac arrhythmia have been reported.However, theresponse of Purkinje fibers to ischemic injury and theirfunctionrolesduring myocardialregenerationare still illusive. Here we introduceda novel inducibleCreallelemouse linethat specificallylabelsthemousecardiac conduction system. Fate mappingshowed Cre activity in different componentsofindicatedspecific labeling ofthe cardiac conduction system, including the sinoatrial and atrioventricularnodes,as well as the Purkinje fibersdifferentknown and unknowncomponents ofthecardiac conductionsystem. RNA-Seqof laser-captured Purkinje fibers showed a uniqueinjuryresponse occurredafterischemic injuryin thisventricularpart of the conductionsystemand corresponding changes in.Ccellularcompositionchange inofPurkinje fibersafter ischemic injury waswereobserved using immunostaining

2021-07-16 | GSE153182 | GEO

Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy

Project description:Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. The developmental origins and mechanistic basis of varying severity of this pathology are unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as a marker upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia.

2018-04-18 | GSE113251 | GEO

Neural Cell Adhesion Molecule (NCAM-1) is Required for Ventricular Conduction System Development

Project description:Cardiac Purkinje cells (PCs) comprise the most distal portion of the ventricular conduction system (VCS) and are essential for synchronous activation of the ventricular myocardium. Contactin-2 (CNTN2), a member of the immunoglobulin superfamily cell adhesion molecules (IgSF-CAMs), was previously identified as a marker of the VCS. Through differential transcriptional profiling we discovered two additional highly enriched IgSF-CAMs in the VCS, NCAM-1 and ALCAM. Immunofluorescence staining showed dynamic expression patterns for each IgSF-CAM during embryonic and early post-natal stages, but ultimately all three proteins became highly enriched in mature PCs. Mice deficient in NCAM-1, but not CNTN2 or ALCAM, exhibited defects in Purkinje cell gene expression and VCS patterning, as well as cardiac conduction disease. Moreover, using ST8sia2 and ST8sia4 knockout mice, we show that inhibition of post-translational modification of NCAM-1 by polysialic acid (PSA) disrupts trafficking of sarcolemmal intercalated disc proteins to Purkinje cell junctional membranes and abnormal expansion of the extracellular space between apposing Purkinje cells. Taken together, our data provide novel insights into the complex developmental biology of the ventricular conduction system.

2021-05-20 | GSE172267 | GEO

Single-cell RNA sequencing of murine hearts for studying the development of the cardiac conduction system

Project description:The development of the cardiac conduction system (CCS) is essential for correct heart function. However, critical details on the cell types populating the CCS in the mammalian heart during the development remain to be resolved. Using single-cell RNA sequencing, we generated a large dataset of transcriptomes of ~0.5 million individual cells isolated from murine hearts at six successive developmental corresponding to the early, middle and late stages of heart development. The dataset provides a powerful library for studying the development of the heart's CCS and other cardiac components. Our initial analysis identified distinct cell types between 20 to 26 cell types across different stages, of which ten are involved in forming the CCS. Our dataset allows researchers to reuse the datasets for data mining and a wide range of analyses. Collectively, our data add valuable transcriptomic resources for further study cardiac development, such as gene expression, transcriptional regulation and functional gene activity in developing hearts, particularly the CCS.

2023-04-26 | GSE230531 | GEO

Single nuclei RNA-seq and snATAC-seq multiome performed in WT and Dhx36 conditional KO hearts at postnatal day 7 (PD7)

Project description:In these experiments, we aimed to investigate the role of cardiomyocyte-specific deletion of the G-quadruplex resolvase Dhx36 in heart development and cardiomyocyte differentiation. To achieve this, we conducted multi-omics analysis using single-nuclei RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) on hearts from postnatal day 7 (PD7) wild-type (WT) and Dhx36 conditional knockout (cKO) mice. Our findings reveal that Dhx36 plays a critical role in the development of the cardiac conduction system (CCS) and in the differentiation of both CCS and working cardiomyocytes

2024-09-15 | E-MTAB-14441 | biostudies-arrayexpress

Single nuclei RNA-seq and snATAC-seq multiome performed in WT and Dhx36 conditional KO hearts at postnatal day 7 (PD7)

2024-09-15 | E-MTAB-14442 | biostudies-arrayexpress