Zebrafish help scientists understand organ regeneration

By The Science Advisory Board staff writers

September 20, 2022 -- For humans damage to the brain, spinal cord, and heart is irreversible, while other species have the ability to regenerate organs. Researchers from the Stowers Institute for Medical Research are studying highly regenerative zebrafish to investigate how their macrophage cells repair and regenerate damaged organs.

Attracted by signals from dying cells, macrophages -- a type of white blood cell -- clean up the damage, rebuild tissue, and make that tissue functional. They first induce inflammation, then follow up with an anti-inflammatory response.

Macrophage anti-inflammatory activation states were previously thought to be linked to just one signaling pathway. However, Stowers postdoctoral researcher Nicolas Denans, PhD, discovered that macrophages must transition through three anti-inflammatory states for successful organ regeneration. The research was published September 20 in the journal Nature Communications.

Zebrafish, tropical freshwater minnows named for their stripes, have transparent embryos, enabling visualization during tissue injury and regeneration. They also have sensory organ hair cells that begin regenerating within five hours after inactivation by antibiotics. This allows researchers to identify the precise timing and genetic programs for each of the three anti-inflammatory macrophage activation states.

Since 70% of human genes are found in zebrafish, regeneration research could potentially help alleviate human conditions that might otherwise require organ transplants and lifelong immunosuppressants.

"Our hypothesis is that human macrophages do not receive the proper chemical activation 'cocktail' to instruct pro-regenerative processes," said Denans. "Identifying the molecular recipe of macrophage activation in zebrafish may one day enable us to design regenerative immunotherapies in humans."

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