Head of the group: Dr. Robert Passier
Researcher scientists: Yann Decker
Main research themes:
- Directed differentiation of human embryonic stem cells to cardiomyocytes
- Understanding the molecular mechanisms of cardiomyocyte differentiation and heart development
- Cardiomyocyte biology and function
- Development of cardiac disease models in human embryonic stem cells
Human embryonic stem cells (hESC) have the capacity to form cardiomyocytes. We have shown that changes in gene expression during hESC-derived cardiomyocyte differentiation faithfully recapitulate the early molecular events during embryonic development. Using hESC as a model for cardiac differentiation in combination with state-of-the-art technology (genomics, transcriptomics, proteomics), we aspire to unravel molecular mechanisms during early cardiac differentiation and heart development. Molecular candidates of interest (e.g. genes, microRNA’s, proteins) are further studied in vitro (picture cardiomyocyte), in different animal models (chick and mouse) (pictures ISH) and, where applicable, in humans. In mice, both cardiac-specific over-expression and (conditional) knockout of candidates are generated.
We are performing gene targeting in hESC, which enables us to generate (Cre-inducible) lineage-specific cell lines, visualized by fluorescent or enzymatic reporters. This allows us to select and purify lineage- and cell-type specific populations (e.g. cardiac progenitor cells and different types of cardiomyocytes), lineage tracing and study molecular events in selected cell populations.
Furthermore, we are developing human cardiac disease models by gene targeting in hESC. In particular, clinically relevant gene mutations or alterations, associated with impaired contractility (cardiomyopathies) and electrophysiology (channelopathies) are generated in hESC. Functional parameters, such as contractility and electrophysiology (performed by the Electrophysiology group) will be measured in cardiomyocytes derived from these transgenic hESC lines and eventually compared to cardiomyocytes from patient-derived induced pluripotent stem cells (see Group Mummery).