Supporting Material for Payumo, AY et al. (2021) Circulation

Newborn mice possess a robust but transient capacity for heart regeneration that is lost when cardiomyocytes (CMs) permanently exit the cell cycle and binucleate during the first week after birth. We discovered that increasing levels of circulating thyroid hormones (THs) observed during the acquisition of endothermy promote postnatal CM cell cycle arrest and limits heart regenerative potential. In this study, we describe novel interactions between adrenergic receptor (AR) and TH signaling regulating thermogenesis, CM proliferation, and heart regeneration. Collectively, our results demonstrate that postnatal AR and TH signaling interactions promote mammalian thermogenesis, inhibit CM cell division, and limit cardiac regenerative capacity.