UCLA

Acquiring pure populations of cardiomyocyte (CM) subtypes is important for developmental studies and necessary for safe cell-based therapies. Here we generated cardiac-specific human embryonic stem cell (hESC) reporter lines to isolate first and second heart field-like CMs (FHF and SHF-like respectively) and cells of the conduction system. Our studies demonstrate that FHF-like CMs can be prospectively isolated based on the co-expression of TBX5/NKX2-5 whereas SHF-like CMs are marked by NKX2-5 but lack TBX5 expression, and finally nodal cells are enriched within the fraction expressing only TBX5. Characterization of these cell populations by electrophysiological, functional, transplantation, and transcriptional studies supports the cellular identity assigned on the basis of NKX2-5 and TBX5 expression.

Furthermore, we identify CORIN as a novel cell surface marker of both FHF-like progenitors and CMs. These results provide a platform to investigate in vitro cardiovascular development and may facilitate a safe approach for cell therapy in heart disease.

In addition to the use of hESC derived cardiomyocyte-like cells to repopulate the heart and fully restore cardiac function after insult, we explore the use direct reprogramming to convert fibroblasts into cardiomyocyte-like cells. Direct cardiac reprogramming using transcription factors, small molecules, miRNAs, and other biologics for the treatment of heart failure have been explored. Here, we focus on the use of modified RNAs and small molecules to develop a safe and efficient method of direct reprogramming for the treatment of heart failure.