Single-cell analysis of γδ thymocyte development in pigs 3403

Abstract Description Swine are an agricultural species of global economic importance. Pigs are also increasingly employed as biomedical models for a variety of human disorders, including immune-related diseases. While pigs and humans have many immunological similarities, the pig immune system is different in several ways, including that pigs have high frequencies of γδ T cells made up of sublineages not found in mice and humans. The reason for this discrepancy is not well understood. Here, we used single cell RNA sequencing to characterize the transcriptional landscape of γδ T cell development in pigs at 60-, 75-, and 90- days of gestation and 1 day and 7 months after birth. We then combined our dataset with publicly available human thymic cells across the same physiological ages to compare γδ T cell development between pigs and humans. We identified common features as well as pig-specific gene signatures and cell states. They include variations between pigs and humans in the timing and expression level of transcription factors, histones, deacetylases, and receptor chains. We also describe gene networks associated with differentiation of the two major subsets of pig γδ T cells, WC1-GATA3loCD2+ and WC1+GATA3hiCD2- cells. Our results provide important clues for why pigs generate high concentrations of γδ T cells. They may also help understand γδ T cell differentiation in mice and humans, which is still not clear, in part because mouse and human γδ thymocytes are rare and thus difficult to study. Funding Sources Supported by NIH/NIAID AI158477; USDA NIFA 2021-67015 Topic Categories Veterinary and Comparative Immunology (VET)