Abstract
The mammalian heart retains regenerative capacity during the early postnatal period, but this ability declines as it matures. Enhancing cardiomyocyte proliferation represents a key therapeutic approach to promote heart regeneration and repair, yet the molecular mechanisms remain elusive. Here, we identified LncBAR (BAF complex-associated lncRNA) as a critical regulator of cardiac regeneration. LncBAR expression declines during heart development but is upregulated following cardiac injury. Loss of LncBAR impairs cardiomyocyte growth, suppresses cell cycle gene expression, and diminishes heart regeneration, as evidenced by reduced cytokinesis and cardiac function. Conversely, cardiac specific overexpression of LncBAR restores cardiomyocyte proliferation and enhances cardiac regeneration, especially in adult myocardial infarction model. Mechanistically, LncBAR interacts with Brg1, stabilizing BRG1 protein level and activating cell cycle progression to drive cardiomyocytes proliferation. Collectively, our study identified LncBAR as a crucial regulator for heart regeneration, highlighting the LncBAR-BRG1 axis as a promising therapeutic strategy for cardiac repair.