Organism-wide contributions to systemic skeletal muscle repair in larval zebrafish.

We developed a systemic muscle injury model in zebrafish. Single cell transcriptomic analysis of muscle and non-muscle tissues revealed that systemic and local muscle injuries elicit distinct cellular molecular responses, both quantitatively and qualitatively. These studies suggest that large- and small-scale muscle injuries activate different regenerative programs, resulting in either systemic or local repair. Overall design: To characterize the regenerative responses and signaling pathways activated after systemic or local muscle injury, we generated Tg(actc1b:NTR-mCherry) transgenic zebrafish lines.At 4 days post fertilization, transgenic larvae were treated with MTZ overnight to systemically injure all myofibers, or were subjected to local mechanical injury (needlestick) of 2-3 somites.Uninjured and systemically injured larvae were collected at 1, 2, and 4 days post injury. Mechanically injured larvae were collected at 2 days post injury. Sequencing results were compared between uninjured, systemically injured, and mechanically injured siblings.