Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 134, Issue -, Pages 69-73Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2019.07.005
Keywords
Binucleated cardiomyocyte; Cell division; Live cell imaging; Centriole; Centrosome; Intermediate multipoles
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Funding
- Emerging Fields Initiative Cell Cycle in Disease and Regeneration (CYDER) (Friedrich-Alexander-University Erlangen-Nurnberg)
- German Research Foundation (DFG) [INST 410/91-1 FUGG, EN453/12-1]
- ELAN Program Grant [ELAN-18-12-17-1-Leone]
- Research Foundation Medicine at the University Clinic Erlangen, Germany
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Background: The majority of adult human, mouse and rat cardiomyocytes is not diploid mononucleated. Nevertheless, the current literature on heart regeneration based on cardiomyocyte proliferation focuses mainly on the proliferation capacity of diploid mononucleated cardiomyocytes, instead of the more abundant mononucleated polyploid or binucleated cardiomyocytes. Here, we aimed at a better understanding of the process of mitosis and cell division in postnatal binucleated cardiomyocytes. Methods and results: Postnatal rat binucleated cardiomyocytes were stimulated to re-enter the cell cycle either by fetal bovine serum or a combination of fibroblast growth factor 1 and p38 MAP kinase inhibitor. Phase-contrast videos revealed that binucleated cardiomyocytes form one metaphase plate and preferentially undergo afterwards cytokinesis failure. The maximum rate of cell division of video-recorded binucleated cardiomyocytes was around 6%. Immunofluorescence analyses of centriole number in mitotic binucleated cardiomyocytes revealed that these cells contain more than four centrioles, which can be paired as well as unpaired. In agreement with multiple and/or unpaired centrioles, multipolar spindle formation was observed in mitotic binucleated cardiomyocytes using fluorescence live imaging of tubulin-GFP. Multipoles were transient and resolved into pseudo-bipolar spindles both in case of cell division and cytokinesis failure. Notably, centrioles were in most cases unevenly distributed among daughter cells. Conclusions: Our results indicate that postnatal binucleated cardiomyocytes upon stimulation can enter mitosis, cope with their multiple and/or unpaired centrioles by forming pseudo-bipolar spindles, and divide.
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