Zebrafish, an emerging model for study hepatic macrophages. (A) Hepatic macrophages are present in the zebrafish liver at both larval and adult stages. (B) Increases in macrophage numbers have been observed in zebrafish models of liver pathology include non-alcoholic liver disease (NAFLD), alcoholic liver disease (ALD), and hepatocellular carcinoma (HCC), as well as in liver regeneration after partial hepatectomy and hepatocyte-specific ablation (left). Involvement of heterogeneous macrophage populations has been implicated in these models (right). (C) Current and potential applications available in zebrafish to study hepatic macrophages. Zebrafish larva is accessible for live imaging, allowing characterization of macrophage behaviors during early stages of immune responses. The live imaging platform in larva can also be utilized for laser-mediated localized manipulations of gene expression and cell ablation. Technologies such as GESTALT (genome editing of synthetic target arrays for lineage tracing) and single cell RNA-sequencing can be utilized to study the ontology and plasticity of macrophages in healthy and injured livers at a population level.
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