Core Findings - The study identifies a crucial subpopulation of injury-induced Clusterin⁺ (Clu⁺) cardiomyocytes that play a key regulatory role in cardiac regeneration in young mammals [3][5] - Clu⁺ cardiomyocytes reprogram macrophages to coordinate repair and anti-inflammatory activities, which is essential for heart regeneration [4][7] - The research reveals that the CLU-TLR4 signaling pathway reprograms macrophages into an anti-inflammatory and repair state, while the CLU-BMP2 signaling axis promotes cardiomyocyte proliferation and restores regenerative capacity in adult hearts [5][7] Mechanisms of Action - After cardiac injury, Clu⁺ cardiomyocytes appear in the marginal areas of the regenerating heart, while they are scarce in non-regenerative contexts [4] - Macrophages secrete CLU, which binds to TLR4 on macrophages, reducing inflammation and promoting repair through Cpt1a-dependent fatty acid oxidation [4] - The study finds that decreased CLU levels in patients with myocardial infarction correlate with impaired cardiac function, while overexpression of CLU or transplantation of engineered Clu⁺ human cardiac organoids enhances myocardial repair in adult mice [4][5] Implications for Future Research - This research provides a new theoretical and technical pathway for cardiac regeneration post-myocardial infarction, highlighting the potential for therapeutic strategies targeting the Clu⁺ cardiomyocyte and macrophage interaction [3][7]