Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes
Author:
Bettencourt-Dias Mónica1, Mittnacht Sybille2, Brockes Jeremy P.1
Affiliation:
1. Department of Biochemistry, University College London, London WC1E 6BT, UK 2. Centre for Cell and Molecular Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, UK
Abstract
Adult newt cardiomyocytes, in contrast to their mammalian counterparts, can proliferate after injury and contribute to the functional regeneration of the heart. In order to understand the mechanisms underlying this plasticity we performed longitudinal studies on single cardiomyocytes in culture. We find that the majority of cardiomyocytes can enter S phase, a process that occurs in response to serum-activated pathways and is dependent on the phosphorylation of the retinoblastoma protein. However, more than half of these cells stably arrest at either entry to mitosis or during cytokinesis, thus resembling the behaviour observed in mammalian cardiomyocytes. Approximately a third of the cells progress through mitosis and may enter successive cell divisions. When cardiomyocytes divided more than once, the proliferative behaviour of sister cells was significantly correlated, in terms of whether they underwent a subsequent cell cycle, and if so, the duration of that cycle. These observations suggest a mechanism whereby newt heart regeneration depends on the retention of proliferative potential in a subset of cardiomyocytes. The regulation of the remaining newt cardiomyocytes is similar to that described for their mammalian counterparts, as they arrest during mitosis or cytokinesis. Understanding the nature of this block and why it arises in some but not other newt cardiomyocytes may lead to an augmentation of the regenerative potential in the mammalian heart.
Publisher
The Company of Biologists
Reference50 articles.
1. Agah, R., Kirshenbaum, L. A., Abdellatif, M., Truong, L. D., Chakraborty, S., Michael, L. H. and Schneider, M. D. (1997). Adenoviral delivery of E2F-1 directs cell cycle reentry and p53-independent apoptosis in postmitotic adult myocardium in vivo. J. Clin. Invest.100, 2722-2728. 2. Anversa, P. and Nadal-Ginard, B. (2002). Myocyte renewal and ventricular remodelling. Nature415, 240-243. 3. Bader, D. and Oberpriller, J. (1979). Autoradiographic and electron microscopic studies of minced cardiac muscle regeneration in the adult newt, notophthalmus viridescens. J. Exp. Zool.208, 177-193. 4. Bader, D. and Oberpriller, J. O. (1978). Repair and reorganization of minced cardiac muscle in the adult newt (Notophthalmus viridescens). J. Morphol.155, 349-357. 5. Barrie, S. E., Eno-Amooquaye, E., Hardcastle, A., Platt, G., Richards, J., Bedford, D., Workman, P., Aherne, W., Mittnacht, S. and Garrett, M. (2003). High throughput screening for the identification of small molecule inhibitors of retinoblastoma protein phosphorylation in cells. Anal. Biochem. (in press).
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