1. Gradual differentiation and confinement of the cardiac conduction system as indicated by marker gene expression
- Author
-
Sonia Stefanovic, Vincent M. Christoffels, Rajiv A Mohan, Vincent W. W. van Eif, Caugant, Julien, University of Amsterdam [Amsterdam] (UvA), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Netherlands Scientific Organization (ZonMW TOP 40-00812-98-12086), Leducq Foundation grant (14CVD01), and Dutch Heart Foundation (COBRA3) (2013T091)., Graduate School, Medical Biology, ACS - Heart failure & arrhythmias, AR&D - Amsterdam Reproduction & Development, ACS - Pulmonary hypertension & thrombosis, and ACS - Amsterdam Cardiovascular Sciences more...
- Subjects
0301 basic medicine ,Genetically modified mouse ,Nervous system ,Genetic Markers ,Transcriptional profiling ,Receptor, EphB3 ,[SDV]Life Sciences [q-bio] ,Context (language use) ,Mice, Transgenic ,030204 cardiovascular system & hematology ,Connexins ,Transcriptome ,03 medical and health sciences ,Calcium Channels, T-Type ,Mice ,0302 clinical medicine ,Heart Conduction System ,Gene expression ,medicine ,Animals ,Humans ,Myocytes, Cardiac ,Expression pattern ,Molecular Biology ,Cardiac conduction system ,Heart development ,Receptors, Notch ,Chemistry ,Myocardium ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Conduction system development ,Cell biology ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,medicine.anatomical_structure ,Calcium Channels ,Electrical conduction system of the heart ,medicine.symptom ,T-Box Domain Proteins ,Muscle contraction ,Signal Transduction ,Working myocardium - Abstract
International audience; The components of the cardiac conduction system, responsible for coordinated activation of the heart chambers, are well defined and their cells differ in gene expression profile and phenotype from those of the surrounding working myocardium. Yet, when and on what basis the myocardium of each of the conduction system components become distinguishable from other myocardium during heart development has not been well established. To identify and assess cell type-specific expression profiles and differentiation markers, we performed transcriptome analysis on fluorescence activated cell sorted purified conduction system (Venus +) and chamber myocardial cells (Katushka +) of Tbx3 +/Venus ;TgNppb(Katushka) double transgenic mouse fetuses. We found that transcripts associated with nervous system development and ion channel activity were enriched in Tbx3 + conduction system cells, whereas transcripts associated with mitochondrial function, muscle contraction and fatty acid metabolism were enriched in the Nppb + working myocardium. We analyzed spatio-temporal expression patterns of several candidate markers (Cacna2d2, Cacna1g, Ephb3, Tnni1), reviewed those of established conduction system markers (Tbx3, Hcn4, Gja5, Cntn2), and placed the patterns in the context of conduction system development. The overview indicates that different properties of conduction system components develop gradually and at different developmental stages, and that chamber myocardium gradually differentiates and diverges from conduction system myocardium until after birth. more...
- Published
- 2019
- Full Text
- View/download PDF