Abstract
The laboratory rat is widely used as a model for human diseases. Many of these diseases involve monocytes and tissue macrophages in different states of activation. Whilst methods for in vitro differentiation of mouse macrophages from embryonic stem cells (ESC) and bone marrow (BM) are well established, these are lacking for the rat. The gene expression profiles of rat macrophages have also not been characterised to the same extent as mouse. We have established the methodology for production of rat ESC-derived macrophages and compared their gene expression profiles to macrophages obtained from the lung and peritoneal cavity and those differentiated from BM and blood monocytes. We determined the gene signature of Kupffer cells in the liver using rats deficient in macrophage colony stimulating factor receptor (CSF1R). We also examined the response of BM-derived macrophages to lipopolysaccharide (LPS). The results indicate that many, but not all, tissue-specific adaptations observed in mice are conserved in the rat. Importantly, we show that unlike mice, rat macrophages express the CSF1R ligand, colony stimulating factor 1 (CSF1).
Highlights
The importance of the laboratory rat as a model for many human diseases, including cardiovascular, neurological, cancer, diabetes, respiratory and inflammatory disease has been widely-recognised [reviewed in [1, 2]]
Macrophage progenitors are collected from the supernatant and plated on non-tissue culture (TC) plastic in colony stimulating factor 1 (CSF1) alone
Embryonic stem cell-derived macrophages (ESDM) are collected a week later [33]. When this method was used for rat embryonic stem cells (ESC) no macrophages were produced
Summary
The importance of the laboratory rat as a model for many human diseases, including cardiovascular, neurological, cancer, diabetes, respiratory and inflammatory disease has been widely-recognised [reviewed in [1, 2]]. The availability of whole genome sequences of multiple rat strains with wellcharacterised genetic disease susceptibility revealed evidence of selective sweeps associated with breeding for the trait, in many cases overlapping human disease susceptibility loci [3]. Many of these diseases involve cells of the mononuclear phagocyte system (monocytes, tissue macrophages) in different states of activation as effectors. The underlying genetic susceptibility to disease has been associated with differences in regulation or function of macrophage-expressed genes.
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