ArticleMolecular and cellular biochemistry2013
Genetic isolation of stem cell-derived pacemaker-nodal cardiac myocytes.
Article in Molecular and cellular biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Towards chamber specific heart-on-a-chip for drug testing applications.Advanced drug delivery reviews · 2020Pooled it
- Local tissue mechanics control cardiac pacemaker cell embryonic patterning.Life science alliance · 2023Article
- Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes.Cells · 2023Article
- Cellular and Molecular Mechanisms of Functional Hierarchy of Pacemaker Clusters in the Sinoatrial Node: New Insights into Sick Sinus Syndrome.Journal of cardiovascular development and disease · 2021Review
- Assembly of the Cardiac Pacemaking Complex: Electrogenic Principles of Sinoatrial Node Morphogenesis.Journal of cardiovascular development and disease · 2021Review
- Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization.International journal of molecular sciences · 2021Article
- Tbx3-Mediated Regulation of Cardiac Conduction System Development and Function: Potential Contributions of Alternative RNA Processing.Pediatric cardiology · 2019Review
- Transcriptional regulation of the cardiac conduction system.Nature reviews. Cardiology · 2018Review
- Development of the cardiac pacemaker.Cellular and molecular life sciences : CMLS · 2017Review
- Overexpression of Map3k7 activates sinoatrial node-like differentiation in mouse ES-derived cardiomyocytes.PloS one · 2017Article
- New Approaches to Biological Pacemakers: Links to Sinoatrial Node Development.Trends in molecular medicine · 2015Review
- Distinct expression patterns of HCN channels in HL-1 cardiomyocytes.BMC cell biology · 2015Article
- Efficient Generation of Cardiac Purkinje Cells from ESCs by Activating cAMP Signaling.Stem cell reports · 2015Article
- Isolation and characterization of embryonic stem cell-derived cardiac Purkinje cells.Stem cells (Dayton, Ohio) · 2015Article
- Article
- Morphology of mouse sinoatrial node and its expression of NF-160 and HCN4.International journal of clinical and experimental medicine · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysfunction of the cardiac pacemaker tissues due to genetic defects, acquired diseases, or aging results in arrhythmias. When arrhythmias occur, artificial pacemaker implants are used for treatment. However, the numerous limitations of electronic implants have prompted studies of biological pacemakers that can integrate into the myocardium providing a permanent cure. Embryonic stem (ES) cells cultured as three-dimensional (3D) spheroid aggregates termed embryoid bodies possess the ability to generate all cardiac myocyte subtypes. Here, we report the use of a SHOX2 promoter and a Cx30.2 enhancer to genetically identify and isolate ES cell-derived sinoatrial node (SAN) and atrioventricular node (AVN) cells, respectively. The ES cell-derived Shox2 and Cx30.2 cardiac myocytes exhibit a spider cell morphology and high intracellular calcium loading characteristic of pacemaker-nodal myocytes. These cells express abundant levels of pacemaker genes such as endogenous HCN4, Cx45, Cx30.2, Tbx2, and Tbx3. These cells were passaged, frozen, and thawed multiple times while maintaining their pacemaker-nodal phenotype. When cultured as 3D aggregates in an attempt to create a critical mass that simulates in vivo architecture, these cell lines exhibited an increase in the expression level of key regulators of cardiovascular development, such as GATA4 and GATA6 transcription factors. In addition, the aggregate culture system resulted in an increase in the expression level of several ion channels that play a major role in the spontaneous diastolic depolarization characteristic of pacemaker cells. We have isolated pure populations of SAN and AVN cells that will be useful tools for generating biological pacemakers.
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