Fang, Y., Gupta, V., Karra, R., Holdway, J.E., Kikuchi, K., and Poss, K.D. (2013) Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration. Proc. Natl. Acad. Sci. USA. 110(33):13416-13421.
Certain lower vertebrates like zebrafish activate proliferation of spared cardiomyocytes after cardiac injury to regenerate
lost heart muscle. Here, we used translating ribosome affinity purification to profile translating RNAs in zebrafish cardiomyocytes
during heart regeneration. We identified dynamic induction of several Jak1/Stat3 pathway members following trauma, events
accompanied by cytokine production. Transgenic Stat3 inhibition in cardiomyocytes restricted injury-induced proliferation
and regeneration, but did not reduce cardiogenesis during animal growth. The secreted protein Rln3a was induced in a Stat3-dependent
manner by injury, and exogenous Rln3 delivery during Stat3 inhibition stimulated cardiomyocyte proliferation. Our results
identify an injury-specific cardiomyocyte program essential for heart regeneration.