Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration. Dev Cell 2020 Apr 06;53(1):42-59.e11
Date
02/29/2020Pubmed ID
32109383Pubmed Central ID
PMC7346764DOI
10.1016/j.devcel.2020.01.030Scopus ID
2-s2.0-85082511708 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
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.
Author List
Han L, Choudhury S, Mich-Basso JD, Ammanamanchi N, Ganapathy B, Suresh S, Khaladkar M, Singh J, Maehr R, Zuppo DA, Kim J, Eberwine JH, Wyman SK, Wu YL, Kühn BAuthor
Lu Han PhD Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Nucleus
Cell Nucleus Division
Cell Proliferation
Cells, Cultured
Heart
Induced Pluripotent Stem Cells
Lamin Type B
Mice
Myocytes, Cardiac
Regeneration
Wound Healing
