The role of mitophagy during hematopoiesis in an invertebrate <i>, Pacifastacus leniusculus</i>

Freshwater crayfish as most aquatic crustaceans live for up to 20-30 years on the bottom of lakes and rivers, constantly exposed to millions of microorganisms. Consequently, they must have an effective immune system to combat and eliminate pathogens. The main immune cells are the hemocytes, and they are regularly consumed during the animal's whole life and are continuously produced through hematopoiesis. We used DMSO as a tool to induce differentiation of hematopoietic stem cells and we can show that differentiation of hematopoietic stem cells to mature hemocytes in a freshwater crayfish is preceded by degradation of mitochondria by mitophagy and this process could be inhibited by a mitophagy inhibitor. The differentiation process was regulated by β-catenin signaling in similarity to differentiation of human neutrophils. A better understanding of the molecular mechanisms that regulate hemocyte development in these animals will provide new insights into the evolution of the innate immune system and hematopoiesis in general.