The study investigates the transient regenerative potential of the neonatal mouse heart. The researchers found that the hearts of 1-day-old neonatal mice can regenerate after partial surgical resection, characterized by cardiomyocyte proliferation with minimal hypertrophy or fibrosis. This regenerative response was distinct from repair processes and was observed within 21 days. Genetic fate mapping indicated that most of the cardiomyocytes in the regenerated tissue originated from preexisting cardiomyocytes. Echocardiography 2 months post-surgery revealed normal systolic function in the regenerated ventricular apex. However, this regenerative capacity was lost by 7 days of age, coinciding with the developmental window when cardiomyocytes become binucleate and withdraw from the cell cycle. The findings suggest that the mammalian heart retains a brief period of regenerative potential after birth, similar to certain fish and amphibians.The study investigates the transient regenerative potential of the neonatal mouse heart. The researchers found that the hearts of 1-day-old neonatal mice can regenerate after partial surgical resection, characterized by cardiomyocyte proliferation with minimal hypertrophy or fibrosis. This regenerative response was distinct from repair processes and was observed within 21 days. Genetic fate mapping indicated that most of the cardiomyocytes in the regenerated tissue originated from preexisting cardiomyocytes. Echocardiography 2 months post-surgery revealed normal systolic function in the regenerated ventricular apex. However, this regenerative capacity was lost by 7 days of age, coinciding with the developmental window when cardiomyocytes become binucleate and withdraw from the cell cycle. The findings suggest that the mammalian heart retains a brief period of regenerative potential after birth, similar to certain fish and amphibians.