Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration

Y Fang, V Gupta, R Karra, JE Holdway… - Proceedings of the …, 2013 - National Acad Sciences
Y Fang, V Gupta, R Karra, JE Holdway, K Kikuchi, KD Poss
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
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 …
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.
National Acad Sciences