Advancing towards a unified eosinophil signature from transcriptional profiling

Abstract Eosinophils are granulocytes that can accumulate in increased numbers in tissues and/or peripheral blood in disease. Phenotyping of eosinophils in health and disease has the potential to improve the precision of diagnosis and choice of therapies for eosinophilic-associated diseases. Transcriptional profiling of eosinophils has been plagued by cell fragility and difficulty isolating high quality RNA. With several technological advances, single-cell RNA sequencing (scRNA-seq) has become possible with eosinophils, at least from mice, while bulk RNA sequencing and microarrays have been performed in both murine and human samples. Anticipating more eosinophil transcriptional profiles in the coming years, we provide a summary of prior studies conducted on mouse and human eosinophils in blood and tissue, with a discussion of the advantages and potential pitfalls of various approaches. Common technical standards in studying eosinophil biology would help advance the field and make cross-study comparisons possible. Knowledge gaps and opportunities include identifying a minimal set of genes that define the eosinophil lineage, comparative studies between active disease and remission vs. homeostasis or development, especially in humans, and a comprehensive comparison between murine and human eosinophils at the transcriptional level. Characterizing such transcriptional patterns will be important to understanding the complex and diverse roles of eosinophils in both health and disease.