Arica Beisaw

Abstract The adult zebrafish heart can regenerate after injury, but the earliest gene expression changes that trigger this process remain poorly understood. Here we show that in vivo single-cell RNA metabolic labeling, which marks newly made RNA in individual cells, can capture rapid responses in the adult zebrafish heart after injury. Within the first 6 h, we detect activation of innate immune programs, including Toll-like receptor signaling, in a subset of macrophage-like immune cells.

Abstract In contrast to mammals, adult zebrafish achieve complete heart regeneration via proliferation of cardiomyocytes. Surprisingly, we found that regenerating cardiomyocytes experience DNA replication stress, which represents one reason for declining tissue regeneration during aging in mammals. Pharmacological inhibition of ATM and ATR kinases revealed that DNA damage response signaling is essential for zebrafish heart regeneration.

Highlights • Mechanical forces from cardiac contractility positively regulate VCL in vivo • VCL interacts with actin regulators in cardiomyocytes in response to mechanical forces • VCL facilitates cardiomyocyte myofilament maturation through SSH1 and CFL • Zebrafish cfl1 mutants exhibit cardiomyocyte myofilament disruption Summary Mechanical forces regulate cell behavior and tissue morphogenesis.