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

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 71081 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 WBspecific 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).