Integrated Single-cell Transcriptomic Map of Pig Kidney Cells Across Various Periods and Anatomical Sites

The kidney plays a crucial role in maintaining fluid, electrolyte, and metabolite balance and in regulating blood pressure. Pig can serve as a human biomedical model, providing key insights into human renal physiology during different physiological phases. We employed Single-cell RNA sequencing to profile 138,469 cells from 12 pig kidney samples across embryonic (E), fattening (F) and pregnancy (P) periods, identifying 29 cell types. We observed PT cells exhibit high expression of metabolism-related transcription factors (TFs) including GPD1, ACAA1 and AGMAT. It has been validated across multiple individuals, periods and species. Fluorescent homologous double labeling staining of paraffin sections further validated the expression of ACAA1 and AGMAT in PT cells. We also do a comparative analysis between pig and human kidneys. It showed that cell type of the same classification demonstrates a greater level of similarity. From the cell type heterogeneity perspective, we highlight the heterogeneity of thick ascending limb (TAL) cells and identified a cluster of TAL cells related to immune function. Then we explored the functional heterogeneity of kidney residual macrophages (KRMs) at different anatomical sites. In renal medulla, KRMs are involved in phagocytosis and leukocyte activation, whereas in renal pelvis, they act as a ligand, recruiting the neutrophil (Neu) with bactericidal activation to migrate to the renal pelvis site to combat urinary tract infections.