The transcriptomics of the ever-changing heart: From development to senescence

The thesis entitles different aspects of cardiac development by looking at the transcriptome during the development. The transcriptome is briefly the second step after the genome and entails all information on the current state of a cell, tissue or organ. Hence, different techniques were used to target the transcriptome during different stages and changes in the lifetime of the human heart. First, aging was investigated by using natural aging and accelerated aging mouse models and found that the accelerated aged models showed more disease or model specific transcriptome, while natural aging was very stable and was mostly affected by immune related pathways. Therefore, early development was accessed by using a rising technique called human induced pluripotent stem cells (hIPSCs). In short, this technique uses human derived cells, which then can be differentiated into cardiomyocytes (CM) that resemble human development. By using a machine learning algorithm, this thesis compared these hiPSC-derived CMs with adult CMs and concluded that indeed hiPSC-derived CMs showed similar transcriptomic patterns and therefore show huge prospects to be used to investigate cardiac predispositions and drug treatment. In summary, this thesis gives important insights to different stages and changes in the lifetime of the human heart.