RRC ID 58454
Author 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 B.
Title Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration.
Journal Dev Cell
Abstract 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.
Volume 53(1)
Pages 42-59.e11
Published 2020-4-6
DOI 10.1016/j.devcel.2020.01.030
PII S1534-5807(20)30062-9
PMID 32109383
PMC PMC7346764
MeSH Animals Cell Nucleus / metabolism Cell Nucleus Division / physiology Cell Proliferation / physiology Cells, Cultured Heart / physiology* Induced Pluripotent Stem Cells / cytology Lamin Type B / metabolism* Mice Myocytes, Cardiac / metabolism* Regeneration / physiology* Wound Healing / physiology
IF 10.092
Times Cited 3
Mice RBRC02706