Postnatal state transition of cardiomyocyte as a primary step in heart maturation
Received date: 02 Oct 2021
Accepted date: 17 Jan 2022
Published date: 15 Nov 2022
Copyright
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 epigenetic and transcriptional decline of cardiac gene expression immediately after birth, leading to a transition 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 perturbed 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.
Key words: heart maturation; state transition; cardiomyocyte; JUN; heart regeneration
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]. Protein & Cell, 2022 , 13(11) : 842 -862 . DOI: 10.1007/s13238-022-00908-4
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