Molecular mechanisms of heart field specific cardiomyocyte differentiation- a computational modeling approach

Tissue engineering protocols achieve building miniature hearts but mechanisms determining cell differentiation still need to be fully understood and optimized. In this study, we present a gene regulatory network (GRN) that describes the differentiation of committed cardiomyocytes towards ventricular or atrial cardiomyocytes. The GRN is coupled with Boolean dynamics and steady state analysis shows steady states which agree with the experimental expression of marker genes. Our Boolean model extends earlier work on a model describing the first and second heart field formation to include atrial and ventricular cardiomyocytes. Thus, our study paves the way for the generation of heart field-specific cardiomyocytes located in specific chambers of the fully developed heart. The Boolean model is validated through simulations and by its ability to reproduce known knockouts.