No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice
Kanar Alkass1, Joni Panula2, Mattias Westman3
1Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden; Department of Forensic Medicine, The National Board of Forensic Medicine, SE-17177 Stockholm, Sweden.
Insights
Heart cell number is established early, with postnatal DNA synthesis driven by multinucleation and polyploidization, not proliferation. This challenges previous findings on cardiomyocyte generation.
Area of Science:
- Cardiology
- Developmental Biology
- Cell Biology
Background:
- The extent of cardiomyocyte generation in adult hearts is debated.
- A prior study suggested a 40% increase in cardiomyocyte number due to proliferation during mouse preadolescence.
Purpose of the Study:
- To investigate the contribution of cardiomyocyte proliferation to postnatal heart growth.
- To re-evaluate the mechanisms driving DNA synthesis in cardiomyocytes after birth.
Main Methods:
- Design-based stereology was employed to assess cardiomyocyte number and DNA synthesis.
- (15)N-thymidine and Bromodeoxyuridine (BrdU) analyses were used to detect cell proliferation.
- Quantitative assessments were performed during postnatal development in mice.
Main Results:
- Cardiomyocyte proliferation accounted for 30% of postnatal DNA synthesis but did not increase cardiomyocyte number after postnatal day 11.
- No proliferative peak was observed in preadolescent mice.
- Cardiomyocyte multinucleation (57%) and nuclear polyploidization (13%) were the primary drivers of postnatal DNA synthesis.
Conclusions:
- The majority of cardiomyocytes are established within the first postnatal week.
- Subsequent DNA synthesis involves non-replicative processes like multinucleation and polyploidization.
- These findings contradict the notion of significant cardiomyocyte proliferation contributing to heart growth in preadolescent mice.
Abstract:
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. (15)N-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.
