PUBLICATION

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

Authors
Rovira, M., Ferrero, G., Miserocchi, M., Montanari, A., Lattuca, R., Wittamer, V.
ID
ZDB-PUB-251212-3
Date
2025
Source
eLIFE   13: (Journal)
Registered Authors
Wittamer, Valerie
Keywords
dendritic cells, evolutionary biology, immune repertoire, microglia, neuroscience, zebrafish
MeSH Terms
  • Animals
  • Brain*/cytology
  • Brain*/immunology
  • Dendritic Cells*/immunology
  • Dendritic Cells*/metabolism
  • Interferon Regulatory Factors/genetics
  • Microglia
  • Myeloid Cells
  • Single-Cell Analysis
  • Transcriptome*
  • Zebrafish*/genetics
  • Zebrafish*/immunology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
41379882 Full text @ Elife
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping