A High-Resolution Cell Atlas of the Domestic Pig Lung and an Online Platform for Exploring Lung Single-Cell Data

Abstract The genetically engineered pig is regarded as an optimal source of human organs for transplantation and an excellent model for human disease research given its comparable physiology to human beings. A myriad of single-cell RNA sequencing (scRNA-seq) data on humans has been reported, but such data on pigs are scarce. Here, we applied scRNA-seq technology to study the cellular heterogeneity of three-month-old pig lungs, generating the single-cell atlas of 13,580 cells covering 16 major cell types. Based on this data, we systematically characterized the similarities and differences in the cellular cross talk and expression patterns of respiratory virus receptors in each cell type of pig lungs compared to human lungs. Furthermore, we analyzed pig lung xenotransplantation barriers and showed the cell type expression patterns of 10 genes associated with pig-to-human immunobiological incompatibility and coagulation dysregulation. We also investigated the conserved TFs and their candidate target genes and constructed five conserved transcription factor regulatory networks in the main cell types shared by pig and human lungs. Finally, we presented a comprehensive and openly accessible online platform, ScdbLung. Our scRNA-seq atlas of the domestic pig lung and ScdbLung database can guide pig lung research and clinical applicability.