This review examines how heart muscle cells (cardiomyocytes) develop polyploidy—having multiple copies of chromosomes—during mammalian development. Unlike zebrafish, mammalian cardiomyocytes lose their ability to divide and become polyploid as they mature. This polyploidization varies significantly between species in timing and degree. Importantly, polyploidy acts as a barrier to heart regeneration after cardiac injury, preventing cardiomyocytes from proliferating to repair damaged tissue. Understanding this process could lead to new therapeutic strategies for heart regeneration.
