Absence of a prolonged macrophage and B cell response inhibits heart regeneration in the Mexican cavefish

The Mexican cavefish provides a unique comparative model to study heart regeneration and scarring within a single species, with Surface fish capable of heart regeneration and their cave-dwelling Pachón counterparts lacking this ability, similar to the human heart.

Using single-cell transcriptomics and immune perturbations, we find significant differences in the immune response between the two populations. Unlike the transient response in the scarring Pachón, the regenerative Surface fish heart generates an unexpected prolonged innate and adaptive immune response, with unique functions at late stages of regeneration. Inhibiting the overall prolonged immune response impairs regeneration and cardiomyocyte proliferation.