Comprehensive methylomes and transcriptomes of tissue-specific and body-size associated genes in miniature pigs

Abstract

The rising demand for organ transplantation far exceeds the supply, with only a small proportion of patients receiving transplants. As a promising solution, minipigs have emerged as valuable models in xenotransplantation due to their physiological similarities to humans, yet the understanding of DNA elements with regulatory functions remains limited. This study provides the first comprehensive transcriptomic and epigenomic map of minipigs, analyzing five tissues (back fat, heart, kidney, liver, and loin) from groups at the ends of a continuum in body size variation. This foundational epigenomic dataset identified tissue-specific genes, revealing key mechanisms underlying physiological and pathological processes such as MYH7B in the heart and ITIH4 in the liver. Genes with differential epigenomic signatures according to the body size variation within minipigs included DES in the heart, which is involved in myofibril linkage and filament formation. Notably, human DNA methylation features in immune-associated genes such as IFI30, NCK2, NFKB1, and SOS2 exhibited stronger epigenomic conservation with minipigs than standard pigs, emphasizing their potential as a closer model for human immune responses. In conclusion, this high-resolution dataset provides a valuable foundation for advancing research in xenotransplantation, organ development, and immune mechanisms, positioning minipigs as a robust model for biomedical applications. © 2025 Elsevier B.V.