期刊
DEVELOPMENTAL CELL
卷 53, 期 1, 页码 42-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2020.01.030
关键词
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资金
- Richard King Mellon Foundation Institute for Pediatric Research (UPMC Children's Hospital of Pittsburgh)
- Transatlantic Network of Excellence grant by Leducq Foundation [15CVD03]
- Children's Cardiomyopathy Foundation
- NIH [R01HL106302, F31HL149148, 1S10OD019942-01]
- Health Research Formula Funds from the Commonwealth of Pennsylvania
- AHA Career Development Awards
- Office of Faculty Development (Boston Children's Hospital)
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.
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