Dynamic single-nucleus transcriptomic profiling of kidney development in Bamaxiang and Wild Boar.

Elucidating the developmental period- and breed-dependent cellular differences of the kidney may provide essential insights for kidney xenotransplantation research, potentially enhancing donor organ selection criteria and improving transplantation outcomes. We utilized single-nucleus transcriptomes to profile 71 081 high-quality nuclei and identified 33 cell types from eight kidney samples collected from Bamaxiang (BMX) and Wild Boar (WB) breeds at three developmental periods (Weaning, Fattening and Maturity). We noticed proximal tubule (PT) cell, principal cell (PC) and thick ascending limb (TAL) cell underwent significant transcriptional changes through developmental period, with PT cells shifting from development-related functions during Weaning period to metabolic and transport functions in Fattening and Maturity period. Through heterogeneity analysis of PT cells, we characterized distinct functional subtypes and identified the PT2 subtype cluster specifically in the mature WB breed which showed enrichment in immune function regulation. We investigated PC cells heterogeneity in BMX pig and WB. In Weaning period, PC0 subtype shared by both breeds showed developmental characteristics. WB-specific PC2 subtype was enriched in temperature regulation pathways. In Maturity period, BMX-specific PC0 subtype showed enrichment in aerobic metabolism, while WB-specific PC1 subtype additionally expressed genes involved in glucose metabolism, reflecting their different adaptations to domestic and natural environments. Cell-cell interaction analysis revealed the EGF signaling pathway as the most active throughout development in BMX pig kidneys, where different epithelial tubule subtypes utilized distinct EGF ligands (BTC, EGF, TGFA) and their corresponding receptors for intercellular communication.