No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice

• Published in: Cell Vol. 163; no. 4; pp. 1026 - 1036
• Main Authors: Alkass, Kanar, Panula, Joni, Westman, Mattias, Wu, Ting-Di, Guerquin-Kern, Jean-Luc, Bergmann, Olaf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.11.2015
• Subjects: Animals; Cell Differentiation; Cell Proliferation; Heart - growth & development; Male; Medicin och hälsovetenskap; Myocytes, Cardiac - cytology
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2015.10.035

The magnitude of cardiomyocyte generation in the adult heart has been heavily debated. A recent report suggests that during mouse preadolescence, cardiomyocyte proliferation leads to a 40% increase in the number of cardiomyocytes. Such an expansion would change our understanding of heart growth and have far-reaching implications for cardiac regeneration. Here, using design-based stereology, we found that cardiomyocyte proliferation accounted for 30% of postnatal DNA synthesis; however, we were unable to detect any changes in cardiomyocyte number after postnatal day 11. 15N-thymidine and BrdU analyses provided no evidence for a proliferative peak in preadolescent mice. By contrast, cardiomyocyte multinucleation comprises 57% of postnatal DNA synthesis, followed by cardiomyocyte nuclear polyploidisation, contributing with 13% to DNA synthesis within the second and third postnatal weeks. We conclude that the majority of cardiomyocytes is set within the first postnatal week and that this event is followed by two waves of non-replicative DNA synthesis. This Matters Arising paper is in response to Naqvi et al. (2014), published in Cell. See also the associated Correspondence by Soonpaa et al. (2015), and the response by Naqvi et al. (2015), published in this issue. [Display omitted] •Cardiomyocyte number expansion is limited to the neonatal period•Multinucleation and ploidisation follow neonatal cardiomyocyte duplication•Cardiomyocyte hypertrophy is sufficient to explain preadolescent heart growth Contrary to a recent report suggesting that a preadolescent burst of cardiomyocyte proliferation promotes heart growth, cardiomyocyte number expansion appears limited to the neonatal period, with cardiomyocyte hypertrophy likely accounting for the increase in the heart size.