Dynamic single-nucleus transcriptomic profiling of kidney development in Bamaxiang pigs and wild boar

Defining developmental periods- and breed-specific cellular features of the porcine kidney is critical for refining donor selection strategies in xenotransplantation. This study utilized single-nucleus RNA sequencing to generate 71 081 high-quality transcriptomes from eight kidneys sampled across three developmental periods—weaning, fattening, and maturity—in Bamaxiang (BMX) and wild boar (WB) breeds. A total of 33 distinct cell types were identified. Proximal tubule (PT), principal (PC), and thick ascending limb (TAL) cells exhibited pronounced transcriptional transitions across developmental periods. PT cells displayed a temporal shift from early development-related functions during the weaning period to metabolic and transport functions during fattening and maturity. Subclustering of PT cells revealed discrete functional subtypes, including a mature WB-specific PT2 cluster enriched in immune function regulation. In PC cells, both breeds expressed a shared PC0 subtype during weaning with signatures of cellular development. The WB-specific PC2 subtype was enriched in thermoregulation pathways, whereas at maturity, the BMX-specific PC0 subtype exhibited transcriptional features associated with oxidative metabolism and the WB-specific PC1 subtype expressed genes involved in glucose metabolism. These findings suggest divergent physiological adaptations to domestication and wild environments. Cell-cell interaction analysis identified the epidermal growth factor (EGF) signaling pathway as the most active across BMX kidney development, with epithelial tubule subtypes engaging in ligand-receptor interactions via ligands, including betacellulin (BTC), EGF, and transforming growth factor-α (TGF-α).