研究人员证明Oct4、Sox2、Klf4和c-Myc（OSKM）的心脏特异性表达能诱导成年的CM去分化，从而赋予成年心脏以再生能力。OSKM的瞬时特异性表达延长了产后小鼠心脏的再生窗口期，并诱导成年心肌细胞（CM）的基因表达程序与胎儿的CM相似。延长OSKM在CM的表达会导致细胞重编程和心脏肿瘤的形成。
在心肌梗塞前和心肌梗塞期间短期表达OSKM可以改善心肌损伤并提高心脏功能，从而表明时间上控制的去分化和重编程可以使哺乳动物的CM细胞周期重新进入，促进心脏再生。
据了解，成年哺乳动物心脏的CM更替非常缓慢，阻碍了受损心肌的再生。相比之下，胎儿心脏显示出相当大的再生潜力，因为存在不太成熟的心肌细胞，它们仍有增殖的能力。
附：英文原文
Title: Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice
Author: Yanpu Chen, Felipe F. Lüttmann, Eric Schoger, Hans R. Schler, Laura C. Zelarayán, Kee-Pyo Kim, Jody J. Haigh, Johnny Kim, Thomas Braun
Issue&Volume: 2021-09-24
Abstract: Cardiomyocyte (CM) replacement is very slow in adult mammalian hearts, preventing regeneration of damaged myocardium. By contrast, fetal hearts display considerable regenerative potential owing to the presence of less mature CMs that still have the ability to proliferate. In this study, we demonstrate that heart-specific expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) induces adult CMs to dedifferentiate, conferring regenerative capacity to adult hearts. Transient, CM-specific expression of OSKM extends the regenerative window for postnatal mouse hearts and induces a gene expression program in adult CMs that resembles that of fetal CMs. Extended expression of OSKM in CMs leads to cellular reprogramming and heart tumor formation. Short-term OSKM expression before and during myocardial infarction ameliorates myocardial damage and improves cardiac function, demonstrating that temporally controlled dedifferentiation and reprogramming enable cell cycle reentry of mammalian CMs and facilitate heart regeneration.
DOI: abg5159
Source: https://www.science.org/doi/10.1126/science.abg5159