Modeling development in vitro with human pluripotent stem cells

Pluripotent stem cells have the potential to generate virtually any cell type of the body, including cardiovascular tissue. This serves as an excellent model for the study of early cardiac development. One of the major obstacles in delineating the exact molecular network that drives human cardiovascular development was the lack of robust and efficient methods to drive human pluripotent stem cells to cardio-vascular derivatives. We developed a robust differentiation method to efficiently differentiate human pluripotent stem cells to cardiovascular lineage. Importantly, our in vitro system faithfully recapitulates molecular events in human embryonic cardiovascular development. We use this as a platform to study the molecular function of lineage-specific lncRNAs and RBPs in the context of human cardiovascular development using human pluripotent stem cells harbouring a variety of variety of cardio-vascular reporters.

Zerbrafish as an in vivo model of cardiac development and regeneration

In order to study the in vivo function of lncRNAs and other novel genetic elements, we use a collection of cardiovascular reporter zebrafish lines. Importantly, zebrafish can fully regenerate the heart even after a 20% ventricular amputation. However, the molecular network essential to activate and sustain cardiac regenerative response remains poorly elucidated. We aim to understand the role of lncRNAs in cardiac regeneration of the zebrafish heart, and hope to apply these principles to human cardiac regeneration.