The Regents of the University of California, San Francisco San Francisco United States
Many lower vertebrate animals and even mammals at early developmental stages possess striking abilities to restore damaged and lost heart tissues. However, most adult mammals examined so far lack robust cardiac regenerative potential. It still remains enigmatic why such a seemingly beneficial trait is lost in animal evolution, and among 6,399 mammalian species whether there are any animals that still retain significant cardiac regenerative potentials. Here we present our pilot work in searching and charactering novel mammalian models with possible but previously unknown cardiac regenerative capability. Our preliminary analyses suggest the existence of unusual cardiac regenerative capability in certain mammals such as naked mole-rats. In this proposal, we will perform analysis of cardiomyocyte ploidy, a proxy of cardiac regenerative potential, in mammalian species, especially those with low metabolic rates and body temperatures. In addition, we will examine cardiomyocyte proliferative and regenerative potential in adult naked mole-rats and even mouse-naked mole-rat interspecies chimeras. Our strategy of exploring and exploiting new organisms for the study of regenerative biology is generalizable and can be applied to discovering animal and plant species with extraordinary yet unreported physiology and capability. We envision that novel mammalian regeneration models will provide new paradigms for investigation of tissue renewal capability of various organs and appendages, and may yield unprecedented insights into the fundamental principles governing tissue regeneration in animal development and evolution.