Single-nucleus transcriptomics of the Wuzhishan miniature pig kidney reveals developmental dynamics and implicates SATB2 in proximal tubule differentiation

The kidney is an essential endocrine organ that maintains homeostasis by regulating fluid-electrolyte balance and blood pressure. The Wuzhishan miniature pig, anatomically and physiologically similar to humans, is a promising biomedical model, yet its renal cellular composition and developmental dynamics remain poorly defined. Here, we constructed the first high-resolution single-nucleus transcriptomic atlas of the Wuzhishan miniature pig kidney, spanning key developmental stages from neonatal to adult. This atlas provides a comprehensive cellular landscape of the pig kidney and captures cell-type composition along with transcriptional dynamics. We identified 12 major renal cell subpopulations and characterized the inter- and intra-cluster heterogeneity of these subpopulations. Proximal tubule cells (PTCs) constituted the predominant subset and displayed distinct temporal transcriptional profiles, with SATB2 implicated as a potential regulator of PTC development and differentiation. scFEA-based metabolic flux analysis further revealed metabolic heterogeneity among PTC subpopulations. Cross‑species comparisons revealed that the renal parenchymal cell composition and intercellular communication networks of the Wuzhishan miniature pig showed high similarity to those of humans. Moreover, PTCs exhibited low transcriptional correlation with other renal cell types within the same species, suggesting specialized functional identity. This study establishes a single-nucleus transcriptomic atlas of the Wuzhishan miniature pig kidney across developmental stages, providing a foundational data resource for studies of pig kidney development and for evaluating the suitability of pigs as a model for human kidney research, and implicating SATB2 as a candidate regulator of PTC differentiation.