Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration
Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration
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DOI：
10.1016/j.devcel.2020.01.030
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发表时间：
2020-04-06
影响因子：
11.8
通讯作者：
Kuhn, Bernhard
中科院分区：
文献类型：
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作者：
Han, Lu;Choudhury, Sangita;Kuhn, Bernhard
心脏再生需要心肌细胞增殖。人们认为多倍体核的形成为心肌细胞增殖建立了屏障，但其机制在很大程度上是未知的。在这里，我们表明，核纤层丝核纤层蛋白B2（Lmnb2），其表达在出生后的小鼠减少，是必不可少的核膜破裂前进展到中期和随后的分裂。失活Lmnb2减少中期进程，这导致在新生小鼠中形成多倍体心肌细胞核，这反过来又减少心肌再生。增加Lmnb2表达促进心肌细胞M期进展和胞质分裂，并改善新生小鼠心肌再生指标。失活人iPS细胞衍生的心肌细胞中的LMNB 2减少了有丝分裂并增加了多倍体核的形成。在患有心脏病的人类婴儿的原代心肌细胞中，修改LMNB 2表达相应地改变了中期进展和子核的倍性。总之，Lmnb2的表达是必不可少的哺乳动物心肌细胞和心脏再生的有丝分裂。
Heart regeneration requires cardiomyocyte proliferation. It is thought that formation of polyploid nuclei establishes a barrier for cardiomyocyte proliferation, but the mechanisms are largely unknown. Here, we show that the nuclear lamina filament Lamin B2 (Lmnb2), whose expression decreases in mice after birth, is essential for nuclear envelope breakdown prior to progression to metaphase and subsequent division. Inactivating Lmnb2 decreased metaphase progression, which led to formation of polyploid cardiomyocyte nuclei in neonatal mice, which, in turn, decreased myocardial regeneration. Increasing Lmnb2 expression promoted cardiomyocyte M-phase progression and cytokinesis and improved indicators of myocardial regeneration in neonatal mice. Inactivating LMNB2 in human iPS cell-derived cardiomyocytes reduced karyokinesis and increased formation of polyploid nuclei. In primary cardiomyocytes from human infants with heart disease, modifying LMNB2 expression correspondingly altered metaphase progression and ploidy of daughter nuclei. In conclusion, Lmnb2 expression is essential for karyokinesis in mammalian cardiomyocytes and heart regeneration.