{'fraction_non_alphanumeric': 0.018050541516245487, 'fraction_numerical': 0.0003281916639317361, 'mean_word_length': 5.927272727272728, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Results Activation of Notch Signaling In Vivo Results in Upregulation of Conduction System – Enriched Genes

Background—Notch signaling has previously been shown to play an essential role in regulating cell fate decisions and differentiation during cardiogenesis in many systems including Drosophila, Xenopus, and mammals. We hypothesized that Notch may also be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells. Methods and Results—In hearts where Notch signaling is activated within the myocardium from early development onward, Notch promotes a conduction-like phenotype based on ectopic expression of conduction system–specific genes and cell autonomous changes in electrophysiology. With the use of an in vitro assay to activate Notch in newborn cardiomyocytes, we observed global changes in the transcriptome, and in action potential characteristics, consistent with reprogramming to a conduction-like phenotype. Conclusions—Notch can instruct the differentiation of chamber cardiac progenitors into specialized conduction-like cells. Plasticity remains in late-stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues. D iseases of the cardiac conduction system (CCS) are a significant cause of morbidity and mortality in which few therapeutic options exist for treatment outside of implan-tation of electronic pacemakers. Limitations of current pacemaker technology include minimal autonomic responsiveness , infection, the potential for contractile dyssynchrony that may contribute to heart failure, and the requirement for lifelong maintenance and replacement, an especially troubling aspect in the pediatric population. Biological pacemakers may eventually represent a viable alternative to electronic devices, even if only under limited circumstances, and proof-of-principle studies suggest initial promise (reviewed in 1). The ability to instruct cardiomyocytes to become conduction like , either through directed differentiation of human embryonic stem cells or induced pluripotent stem cells, or through direct reprogramming of cardiomyocytes in vivo into conduction-like cells, may be an evolving paradigm for reversing or treating degenerative conduction disease. Deciphering signals that can instruct cardiomyocytes to adopt a conduction phenotype is a prerequisite for progress with this therapeutic approach. The CCS consists of the sinoatrial node, which generates impulses that travel through atrial tissue to arrive at the atrioventricular (AV) node. At the AV node, there is a delay in impulse propagation to allow the atria to contract. Impulses then travel rapidly through the ventricular conduction system, which comprises the His bundle, right and left bundle branches, and peripheral Purkinje fiber network that coordinates activation of the heart from apex to base. Cells of the CCS can be identified as distinct from atrial and ventricular working or chamber myocardium based on unique action potential …