Defining the regulatory signals influencing the pacemaker cell fate – REPACE

The sinoatrial node (SAN) is composed of specialized cells able to generate a spontaneous electric activity allowing cardiac contraction. Congenital or acquired SAN dysfunction results in bradycardia and sudden death. The generation of pacemaker cells by reprogramming gains interest, since biological pacemakers may overcome the shortcomings of the currently used electronic devices. Insight into the molecular biology of pacemaker cells will improve the robustness of pacemaker cell therapies for application in humans. Our preliminary results indicate that HOX transcription factors may be able to promote differentiation towards a pacemaker cell fate. REPACE proposes through a series of tasks to provide a detailed map of pacemaker specific enhancers dependent on HOX transcription factors. To achieve this objective, REPACE will integrate recently developed regulome mapping technologies.