Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling

• DOI: 10.1073/pnas.2008861118
• Publication Date: 2020-12-23T21:38:53Z
• Authors: Yuxuan Guo; Yangpo Cao; Blake D. Jardin; Isha Sethi; Qing Ma; Behzad Moghadaszadeh; Emily C. Troiano; Neil Mazumdar; Michael A. Trembley; Eric M. Small; Guo-Cheng Yuan; Alan H. Beggs; William T. Pu
• Keywords: Cell Nucleus; Sarcomeres; 0301 basic medicine; Serum Response Factor; Mitochondria; Mice; 03 medical and health sciences; Gene Expression Regulation; Mutation; Morphogenesis; Trans-Activators; Animals; Actinin; Myocytes, Cardiac; Cytoskeleton; Signal Transduction; Transcription Factors

Significance Mature cardiomyocytes are highly adapted to pump efficiently over billions of cycles. The mechanisms that regulate and coordinate the acquisition of the specialized features of mature cardiomyocytes in the postnatal period are not well understood. This knowledge gap hinders studies of disease pathogenesis and the maturation of stem cell–derived cardiomyocytes for cardiac regenerative medicine. Here, we studied the roles of sarcomeres, the contractile machinery of cardiomyocytes, in regulating cardiomyocyte maturation. Using an in vivo genetic mosaic approach to circumvent animal lethality and secondary consequences of cardiac dysfunction, we analyzed the contribution of sarcomeres to cardiomyocyte maturation in a physiological context. We identified an important role of sarcomeres in the regulation of signal transduction and gene transcription.