Transcriptional profiling of constitutive mast cells reveals a unique gene expression signature and highlights their heterogeneity across tissues (HYP4P.303)

Abstract

Abstract Constitutive mast cells (MC) are long-lived sentinel cells residing in peripheral connective tissue near the microvasculature and nerve endings. Similar to basophils (Ba), MC express the high-affinity IgE receptor FcεR1α, and are frequently implicated in the pathobiology of allergic diseases. Although protease expression in murine MC varies between tissues, the full extent of their diversity across compartments is not known, and the study of MCs is hindered by their rarity and location. In collaboration with the Immunological Genome Project, we developed techniques for isolating MC from a wide variety of murine tissues for microarray analysis. Hierarchical clustering and principal component analysis of MC versus Ba and other immune cells indicate that Ba are transcriptionally more similar to other circulating granulocytes (eosinophils, and neutrophils) than to MC. Furthermore, granulocytes and other tissue resident myeloid cells (macrophages and dendritic cells) are closer to each other and to lymphoid cells than either group is to constitutive MC. Further analysis revealed a core MC transcriptional signature not seen in other immune cell populations, but MC heterogeneity across tissue compartments was similar to that seen with dendritic cells, indicating that their diversity goes far beyond protease expression. Our results provide novel insights into this unique cell type and lay the groundwork for future studies on the activation and function of MC in peripheral tissue.