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bioRxiv · 10.1101/2023.07.27.550829

A single-cell transcriptomic atlas reveals resident dendritic-like cells in the zebrafish brain parenchyma

Rovira, M.·Ferrero, G.·Miserocchi, M.·Montanari, A.·Wittamer, V.
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Abstract

Recent studies have highlighted the heterogeneity of the immune cell compartment within the steady-state murine and human CNS. However it is not known whether this diversity is conserved among non mammalian vertebrates, especially in the zebrafish, a model system with increasing translational value. Here, we reveal the complexity of the immune landscape of the adult zebrafish brain. Using single-cell transcriptomics, we characterized these different immune cell subpopulations, including cell types that have not been -or have only been partially-characterized in zebrafish so far. By histology, we found that, despite microglia being the main immune cell type in the parenchyma, the zebrafish brain is also populated by a distinct myeloid population that shares a gene signature with mammalian dendritic cells (DC). Notably, zebrafish DC-like cells rely on batf3, a gene essential for the development of conventional DC1 in the mouse. Using specific fluorescent reporter lines that allowed us to reliably discriminate DC-like cells from microglia, we quantified brain myeloid cell defects in commonly used irf8-/-, csf1ra-/- and csf1rb-/- mutant fish, revealing previously unappreciated distinct microglia and DC-like phenotypes. Overall, our results suggest a conserved heterogeneity of brain immune cells across vertebrate evolution and also highlights zebrafish-specific brain immunity characteristics.

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Rovira, M., Ferrero, G., Miserocchi, M., Montanari, A., Wittamer, V.. 2023-07-28. A single-cell transcriptomic atlas reveals resident dendritic-like cells in the zebrafish brain parenchyma. https://doi.org/10.1101/2023.07.27.550829

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