Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration

Dev Cell. 2020 Apr 6;53(1):42-59.e11. doi: 10.1016/j.devcel.2020.01.030. Epub 2020 Feb 27.

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.

Keywords: Lamin B2; Lmnb2; cardiomyocytes; heart injury; karyokinesis; mitosis; myocardial regeneration; polyploidy; terminal differentiation; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Lamin Type B
  • lamin B2