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  • Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration.

Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration.

Developmental cell (2020-02-29)
Lu Han, Sangita Choudhury, Jocelyn D Mich-Basso, Niyatie Ammanamanchi, Balakrishnan Ganapathy, Sangita Suresh, Mugdha Khaladkar, Jennifer Singh, Rene Maehr, Daniel A Zuppo, Junhyong Kim, James H Eberwine, Samuel K Wyman, Yijen L Wu, Bernhard Kühn
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Rat IgG (H+L), highly cross-adsorbed, CF 488A antibody produced in donkey, ~2 mg/mL, affinity isolated antibody
Sigma-Aldrich
Anti-GAPDH antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-α-Actinin (Sarcomeric) antibody produced in mouse, clone EA-53, ascites fluid
Sigma-Aldrich
Anti-Lamin A/C Antibody, clone 14, clone 14, Upstate®, from mouse
Sigma-Aldrich
Anti-Rat IgG (H+L), highly cross-adsorbed, CF 568 antibody produced in donkey, ~2 mg/mL, affinity isolated antibody