Integrated single-cell transcriptomic map of pig kidney cells across various periods and anatomical sites

The kidney is essential for maintaining fluid, electrolyte, and metabolite homeostasis, and for regulating blood pressure. The pig serves as a valuable biomedical model for human renal physiology, offering insights across different physiological states. In this study, single-cell RNA sequencing was used to profile 138 469 cells from 12 pig kidney samples collected during the embryonic (E), fattening (F), and pregnancy (P) periods, identifying 29 cell types. Proximal tubule (PT) cells exhibited elevated expression of metabolism-related transcription factors (TFs), including GPD1, ACAA1, and AGMAT, with validation across multiple individuals, periods, and species. Fluorescence homologous double-labeling of paraffin sections further confirmed the expression of ACAA1 and AGMAT in PT cells. Comparative analysis of pig and human kidneys revealed a high degree of similarity among corresponding cell types. Analysis of cell-type heterogeneity highlighted the diversity of thick ascending limb (TAL) cells, identifying a TAL subpopulation related to immune function. Additionally, the functional heterogeneity of kidney-resident macrophages (KRM) was explored across different anatomical sites. In the renal medulla, KRM were implicated in phagocytosis and leukocyte activation, whereas in the renal pelvis, they functioned as ligands, recruiting neutrophils with bactericidal activity to the renal pelvis to combat urinary tract infections.