Pigs are globally important agricultural and economic animals, and due to their physiological and anatomical structures similar to humans in terms of skin, respiratory, intestinal, and urinary systems, they have become an ideal model for studying human viral diseases. Single-cell RNA sequencing (scRNA-seq) is capable of revealing the specific functions and dynamic changes of different cell subpopulations in tissues, emerging as a powerful tool for dissecting disease mechanisms, developmental trajectories, and immune responses in pigs, and it has been increasingly applied in porcine research. This article systematically reviews the research progress of scRNA-seq technology in three aspects of pig research: decoding disease mechanisms, exploring developmental biology, and analyzing immunological characteristics. It deciphers the heterogeneous responses of porcine cell subpopulations and the dynamic regulation of cell transcriptomes following viral infection, investigates the mechanisms underlying cell lineage differentiation and development during pig growth as well as their associations with disease susceptibility, and elaborates on the dynamic changes of immune cells and immune repertoires along with their correlations with viral infection and vaccine responses. Furthermore, we analyze the technical challenges that this technology still faces, including the incompleteness of pig reference genome annotation, difficulties in sample acquisition and processing, and the complexity of data analysis. We also discuss future application prospects, aiming to provide research insights for scRNA-seq to play a greater role in the prevention and control of pig infectious diseases, genetic breeding, and the development of biomedical models. • ScRNA-seq reveals unprecedented cellular heterogeneity in porcine viral infections. • Single-cell profiling establishes pigs as superior models for human immunological research. • Integrated scTCR/BCR-seq provides novel insights into adaptive immune responses. • ScRNA-seq analysis shows marked similarities between porcine and human immune cells. • The Pig Cell Atlas requires multi-omics integration and spatial transcriptomics.
Liu et al. (2026) studied this question.