Postnatal heart maturation Is the basis of normal cardiac function and provides critical insights into heart repair and regenerative medicine.While static snapshots of the maturing heart have provided much Insight into its molecular signatures,few key events during postnatal cardiomyocyte maturation have been uncovered.Here,we report that cardiomyocytes(CMs)experience epige-netic and transcriptional decline of cardiac gene expression immediately after birth,leading to a transi-tion state of CMs at postnatal day 7(P7)that was essential for CM subtype specification during heart maturation.Large-scale single-cell analysis and genetic lineage tracing confirm the presence of transition state CMs at P7 bridging immature state and mature states.Silencing of key transcription factor JUN In P1-hearts significantly repressed CM transition,resulting in per-turbed CM subtype proportions and reduced cardiac function in mature hearts.In addition,transplantation of P7-CMs into infarcted hearts exhibited cardiac repair potential superior to P1-CMs.Collectively,our data uncover CM state transition as a key event in postnatal heart maturation,which not only provides insights into molecular foundations of heart maturation,but also opens an avenue for manipulation of cardiomyocyte fate in disease and regenerative medicine.

Zheng Li;Fang Yao;Peng Yu;Dandan Li;Mingzhi Zhang;Lin Mao;Xiaomeng Shen;Zongna Ren;Li Wang;Bingying Zhou

Shenzhen Key Laboratory of Cardiovascular Disease,Fuwai Hospital Chinese Academy of Medical Sciences,Shenzhen 518057,China;State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China;Key Laboratory of Pluripotent Stem Cells in Cardiac Repair and Regeneration,Chinese Academy of Medical Sciences,Beijing 100037,China;State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,People's Republic of China

蛋白质与细胞

[1]Zheng Li;Fang Yao;Peng Yu;Dandan Li;Mingzhi Zhang;Lin Mao;Xiaomeng Shen;Zongna Ren;Li Wang;Bingying Zhou-.Postnatal state transition of cardiomyocyte as a primary step in heart maturation)[J].蛋白质与细胞,2022(11):842-862

epige,infarcted

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