biostudies-literatureZhou LHKey Clinical Frontier Technology Project of the Department of Science and Technology of JiangsuInnovative Research Group Project of the National Natural Science Foundation of ChinaNational Natural Science Foundation of Chinae05820https://www.ebi.ac.uk/biostudies/studies/S-EPMC12767070biostudies-literatureUnknown13(1)The neonatal heart possesses the unique ability to regenerate post-injury. Underlying related mechanisms and reactivation of this process are crucial for regeneration medicine. Using quantitative proteomics with tandem mass tag labeling, RNA-sequencing (RNA-seq) and single-nucleus RNA-seq dataset analyses, high mobility group box 2 (HMGB2) is identified as a key regulator of cardiomyocyte proliferation, whose expression declines during postnatal heart development and increases in the high regenerative potential cardiomyocyte populations in hearts post-injury. Cardiomyocyte-specific HMGB2 knockdown curtails cardiomyocyte proliferation and impairs heart regeneration following apical resection in neonatal mice, while cardiomyocyte-specific HMGB2 overexpression enhances cardiomyocyte proliferaAdvanced science (Weinheim, Baden-Wurttemberg, Germany)HMGB2 Promotes Cardiomyocyte Proliferation and Heart Regeneration Through MTA2-Driven Metabolic Reprogramming.PMC12767070BE20228068212100182370344Zhang XZWang LSJing PChen YXBao YLWang HWang SBZhao YXie LPYang TTZhou LHGu LFShan TKHe YDu CWang QMChen JYJi YfalseHMGB2 Promotes Cardiomyocyte Proliferation and Heart Regeneration Through MTA2-Driven Metabolic Reprogramming.The neonatal heart possesses the unique ability to regenerate post-injury. Underlying related mechanisms and reactivation of this process are crucial for regeneration medicine. Using quantitative proteomics with tandem mass tag labeling, RNA-sequencing (RNA-seq) and single-nucleus RNA-seq dataset analyses, high mobility group box 2 (HMGB2) is identified as a key regulator of cardiomyocyte proliferation, whose expression declines during postnatal heart development and increases in the high regenerative potential cardiomyocyte populations in hearts post-injury. Cardiomyocyte-specific HMGB2 knockdown curtails cardiomyocyte proliferation and impairs heart regeneration following apical resection in neonatal mice, while cardiomyocyte-specific HMGB2 overexpression enhances cardiomyocyte prolifera2026-01-01T00:00:00Z2026 Jan2026-06-06T11:05:35.84Z2026-05-29T03:13:02.431ZS-EPMC127670704109237610.1002/advs.202505820