The electrophysiological signatures of the myocardium in cardiac structures, such as the atrioventricular node, pulmonary veins or the right ventricular outflow tract, are established during... Show moreThe electrophysiological signatures of the myocardium in cardiac structures, such as the atrioventricular node, pulmonary veins or the right ventricular outflow tract, are established during development by the spatial and temporal expression of transcription factors that guide expression of specific ion channels. Genome-wide association studies have shown that small variations in genetic regions are key to the expression of these transcription factors and thereby modulate the electrical function of the heart. Moreover, mutations in these factors are found in arrhythmogenic pathologies such as congenital atrioventricular block, as well as in specific forms of atrial fibrillation and ventricular tachycardia. In this review, we discuss the developmental origin of distinct electrophysiological structures in the heart and their involvement in cardiac arrhythmias. Show less
Chiara, V. della; Daxinger, L.; Staal, F.J.T. 2021
Hematopoietic multipotent progenitors seed the thymus and then follow consecutive developmental stages until the formation of mature T cells. During this process, phenotypic changes of T cells... Show moreHematopoietic multipotent progenitors seed the thymus and then follow consecutive developmental stages until the formation of mature T cells. During this process, phenotypic changes of T cells entail stage-specific transcriptional programs that underlie the dynamic progression towards mature lymphocytes. Lineage-specific transcription factors are key drivers of T cell specification and act in conjunction with epigenetic regulators that have also been elucidated as crucial players in the establishment of regulatory networks necessary for proper T cell development. In this review, we summarize the activity of transcription factors and epigenetic regulators that together orchestrate the intricacies of early T cell development with a focus on regulation of T cell lineage commitment. Show less
