10:00 - 12:45
Tue-Epigenetics and RNA
Room: Large Conference Room
Chair/s:
Marco Osterwalder, Nadia Mercader
Regulation of cardiomyocyte proliferation by LncRNA CARMN during heart regeneration in zebrafish
Presented by: Mukesh Kumar Lalwani
Presentation time:  
Mukesh Kumar Lalwani
Queens Medical Research Institute, BHF Centre for Cardiovascular Sciences, University of Edinburgh, UK
Long non-coding RNAs (LncRNAs) are important regulators of gene expression and function. Their functional contribution to the pathophysiology of various cardiovascular diseases, including myocardial infarction (MI), is becoming increasingly clear. During MI, heart muscle undergoes irreversible damage that impairs heart function and eventually leads to heart failure. Although, cardiomyocyte (CM) proliferation is rare in adult humans, in lower vertebrates such as zebrafish, MI stimulates CM proliferation and, in general, efficient myocardium regeneration. Elucidating the molecular mechanisms that govern CM proliferation is key to identify potential targets for therapeutic intervention. Here, we are investigating the role of lncRNA CARdiac Mesoderm Enhancer-associated Noncoding RNA (CARMN) in CM proliferation during heart regeneration in zebrafish. CARMN is expressed in primary cardiac progenitor cells (CPCs), where upon induction of notch signalling it is responsible for cell fate determination to smooth muscle cells or CMs. Our pilot data has, however, found that CARMN has conserved CM nuclear expression pattern in adult zebrafish as well as mouse and human cardiac tissues. In addition, expression of the human CARMN analogue in zebrafish is significantly enhanced and colocalised with proliferating cardiac cells proximal to the zone of myocardial injury, clearly linking to its potential role in CM proliferation and, thereby heart regeneration. Furthermore, we have made CARMN zebrafish mutant using CRISPR gene editing. These mutants have altered expression of proximal loci and syntenic genes in adult cardiac tissue suggesting its RNA dependent regulatory activity. We are further investigating CM proliferation upon injury in CARMN mutants, which is in progress. Our data suggests that CARMN could be an important regulator of CMs proliferation in injury conditions and might be a novel driver of cardiac regeneration in zebrafish, and ultimately in adult mammalian systems.