Interdependent changes of nuclear lamins, nuclear pore complexes, and ploidy regulate cellular regeneration and stress response in the heart

ABSTRACT

In adult mammals, many heart muscle cells (cardiomyocytes) are polyploid, do not proliferate (post-mitotic), and, consequently, cannot contribute to heart regeneration. In contrast, fetal and neonatal heart muscle cells are diploid, proliferate, and contribute to heart regeneration. We have identified interdependent changes of the nuclear lamina, nuclear pore complexes, and DNA-content (ploidy) in heart muscle cell maturation. These results offer new perspectives on how cells alter their nuclear transport and, with that, their gene regulation in response to extracellular signals. We present how changes of the nuclear lamina alter nuclear pore complexes in heart muscle cells. The consequences of these changes for cellular regeneration and stress response in the heart are discussed.

KEYWORDS:

• Cardiac hypertrophy
• cardiac remodeling
• cardiomyocyte
• heart regeneration
• nuclear lamina
• nuclear pore
• nuclear transport

Acknowledgments

We thank members of the Kuhn laboratory and Quasar Padiath (School of Public Health, University of Pittsburgh) for support, helpful discussions, and critical reading of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

All authors prepared the manuscript concept, outline, and draft. All authors reviewed and edited the manuscript.

Additional information

Funding

Research leading to this paper was supported by the Richard King Mellon Foundation Institute for Pediatric Research (UPMC Children’s Hospital of Pittsburgh), NIH grants R01HL151415, R01 HL151386, and R01HL155597, and a grant from the UPMC Aging Institute (to B.K.) and R01HD101574 and R01HD109347 (to M.R.W.M.). This project was supported by an NIH-Training Grant (to Y.L., T32HL129949).