Deciphering the Evolution of Vertebrate Immune Cell Types with Single-Cell RNA-Seq

Single-cell RNA-seq is revolutionizing our understanding of the cell type heterogeneity and evolution in many fields of biology, ranging from neuroscience to cancer to immunology. In immunology, one of the main promises of this approach is the ability to define cell types as clusters in the whole transcriptome space (i.e., without relying on specific surface markers), thereby providing an unbiased classification of immune cell types. So far, this technology has been mainly applied in mouse and human. However, technically it could be used for immune cell type identification in any species without requiring the development and validation of species-specific antibodies for cell sorting. Here, we review recent developments using single-cell RNA-seq to characterize immune cell populations in non-mammalian vertebrates, with a focus on zebrafish (Danio rerio). We advocate that single-cell RNA-seq technology is likely to provide key insights into our understanding of the evolution of the adaptive immune system.