ROLE OF STAT3 FROM EMBRYONIC STEM CELL INTO CARDIAC LINEAGE DIFFERENTIATION AND ITS CARDIOPROTECTIVE ROLE IN ADULT HEART

Abstract

IN VITRO-DERIVED CARDIOMYOCYTES ARE IDEAL FOR USE IN CELL REPLACEMENT THERAPY. HOWEVER, THE TRANSITION FROM BENCH TO BED NECESSITATES A DEEPER UNDERSTANDING OF THE REGULATORY NETWORKS OF EARLY CARDIOMYOCYTE DIFFERENTIATION AS IT TAKES PLACE IN THE EARLY DEVELOPMENT OF EMBRYO. STUDIES HAVE DEMONSTRATED THAT STAT3 IS ESSENTIAL FOR INITIAL STAGES OF CARDIOMYOGENESIS. DESPITE THE IMPORTANT ROLE OF STAT3 IN CARDIOMYOGENESIS, FEW STUDIES HAVE EXPLORED THAT THE ROLE OF STAT3 IN EARLY CARDIOMYOCYTE DIFFERENTIATION BECAUSE CONVENTIONAL STAT3 KO IS EMBRYONIC LETHAL AT THE TIME OF FORMATION OF CARDIOMYOCYTE. IN THIS STUDY, WE HAVE ESTABLISHED AN IN VITRO INDUCIBLE STAT3 KNOCK OUT AND PSTAT3 OVEREXPRESSED ES CELLS SYSTEM IN WHICH STAT3 EXPRESSION CAN BE TEMPORALLY AND SPECIFICALLY DELETED OR OVEREXPRESSED BY DOXYCYCLIN STIMULATION TO ALLOW THE STUDY OF STAT3 FUNCTION DURING EARLY CARDIOMYOCYTE DIFFERENTIATION.