Circadian networks in stem cells and their cardiac derivatives

Abstract

Cardiovascular diseases remain a leading cause of death in Western countries, and are influenced by diurnal rhythms that result in oscillatory gene expression in the heart. Indeed, the circadian clock has been shown to determine the functionality of cardiomyocytes, with detrimental consequences when rhythmicity is disturbed. In vitro differentiation of pluripotent stem cells towards the cardiac lineage is well described, and allows for the derivation of an inexhaustible source of cardiomyocytes for the investigation of heart development and function. Moreover, cardiac stem cell derivatives can be used for drug screenings as well as be tested for their potential to regenerate the heart after injury such as myocardial infarction and heart failure. Whether and how knowledge on circadian rhythms could be applied to optimize applications of stem cell-derived cardiomyocytes in vitro as well as in vivo remains largely unknown, however. In this thesis, we study the role of clock factors and circadian networks in mouse and human embryonic stem cells and their cardiac derivatives.