A unique macrophage subpopulation signals directly to progenitor cells to promote regenerative neurogenesis in the zebrafish spinal cord.

摘要: Central nervous system injury re-initiates neurogenesis in anamniotes (amphibians and fishes), but not mammals. Activation of the innate immune promotes regenerative neurogenesis, it is fundamentally unknown whether this indirect through activation known developmental signaling pathways or cells directly signal to progenitor using mechanisms that are unique regeneration. Using single-cell RNA-seq macrophages, as well cell-type-specific manipulations, we provide evidence for a direct axis from specific lesion-activated macrophages spinal promote zebrafish. Mechanistically, TNFa pro-regenerative induces Tnfrsf1a-mediated AP-1 activity progenitors increase regeneration-promoting expression hdac1 neurogenesis. This establishes principle communicate via non-developmental signals after injury, providing potential targets future interventions regeneration-deficient cord