生物
心脏发育
表观遗传学
过渡(遗传学)
移植
干细胞
心脏移植
转录因子
基因沉默
再生医学
胚胎干细胞
细胞生物学
内科学
遗传学
基因
医学
作者
Li Zheng,Fang Yao,Yu Peng,Dandan Li,Mingzhi Zhang,Lin Mao,Xiaomeng Shen,Zongna Ren,Li Wang,Bingying Zhou
出处
期刊:Protein & Cell
[Springer Nature]
日期:2022-04-08
卷期号:13 (11): 842-862
被引量:5
标识
DOI:10.1007/s13238-022-00908-4
摘要
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.
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