Nearly 1% of all live births are impacted by congenital heart disease (CHD) and over 500 regions of our DNA are associated with cardiovascular disease (CVD). These facts indicate the important role DNA plays in heart health, from developing embryos to adults. By learning how different DNA regions are “turned on/off” in heart cells throughout development and over time, researchers may identify factors that influence heart disease and how heart disease may be treated. However, these studies are challenging as there is a question of how developing heart cells used in research experiments compare to those found in a developing embryo.

Research supported by the Common Fund 4D Nucleome (4DN) program from the lab of Dr. Charles Murry provided an important step in overcoming these challenges. Dr. Murry and his colleagues integrated several research techniques, some of which were developed by the 4DN program, to show that derived human heart cells used in research experiments were very similar to naturally occurring cells with respect to the 3-dimensional architecture of all their DNA – or genomes – and whether certain genes were turned on or off. This information gives researchers confidence when using derived cells in experiments that model diseases of the heart. Overall, the methods developed in this research represent a valuable resource for the study of both heart development and heart disease by revealing genome-wide changes in developing heart cells as well as the dynamics of different DNA regions and which genes are active at different times.

Reference

• Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory. Bertero A, Fields P, Ramani V, Bonora G, Yardimci G, Reinecke H, Pabon L, Noble W, Shendure J, Murry C. Nature Communications, 2019. doi: 10.1038/s41467-019-09483-5