Transcriptional changes in stem cell-derived cardiomyocytes during extended cell cultures

Sammanfattning: The recent advancement in the field of stem cell research gave rise to high expectations from both general and scientific audiences, and indeed, stem cells and stem cell-derived cells have an enormous potential to forward the fields of medical research and regenerative medicine. Nevertheless, there are still many obstacles and limitations associated with stem cell technology. One of those limitations is that currently no method to derive fully mature cardiomyocytes from human pluripotent stem cell is available. Instead, stem cell-derived cardiomyocytes only show basic characteristics of their adult counterparts and are thus only of limited use. However, there is experimental evidence that those cells may increase in maturity during extended culture times. To improve the understanding of those processes, a characterisation of the transcriptional changes in human embryonic stem cell-derived cardiomyocytes over two weeks was made. Using standard bioinformatics methods, including differential and enrichment analysis as well as basic machine learning technologies, changes in mRNA and miRNA transcription and several functions related to those changes could be identified. The analyses indicated increasing structural organisation in the cell cultures, increasing expression of cardiac ion channels and decreasing proliferative capacity in the cardiomyocyte cultures. Furthermore, potential dysregulations of important signalling pathways were observed. The results of this project may aid in developing protocols for differentiating stem cells into cardiomyocytes with features that are more mature than those of the currently available stem cell derived-cardiomyocytes.