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Publication : Gradual differentiation and confinement of the cardiac conduction system as indicated by marker gene expression.

First Author  van Eif VWW Year  2020
Journal  Biochim Biophys Acta Mol Cell Res Volume  1867
Issue  3 Pages  118509
PubMed ID  31306714 Mgi Jnum  J:285325
Mgi Id  MGI:6392473 Doi  10.1016/j.bbamcr.2019.07.004
Citation  van Eif VWW, et al. (2020) Gradual differentiation and confinement of the cardiac conduction system as indicated by marker gene expression. Biochim Biophys Acta Mol Cell Res 1867(3):118509
abstractText  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.
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