Landscape of microenvironment in Randall's plaque by single-cell sequencing

Randall's plaque is significantly associated with occurrence of nephrolithiasis. However, the microenvironment of Randall's plaque is poorly characterized. To investigate the microenvironment of Randall's plaque, we analyzed single-cell RNA data of 3 Randall's plaque and 3 normal renal papillae tissue and identified 11 different cell types. We screened differentially expressed genes among all cell types between Randall's plaque and normal renal papillae. The microenvironment showed two cell types with multiple stone formation-associated transcriptomic programs. Contrary to previous studies, we did not observe macrophages M1/M2 imbalance. Notably, we detected ossification-associated macrophage is enrich in Randall's plaque and validated GPNMB and ACP5 were potential biomarkers on osteoblasts-associated macrophage. We also identified an endothelial subset harboring active communication (COL15A1+ PCDH17+ endothelial, DPECs) with other cells. Together with Immunofluorescence, we validated ossification-associated macrophage and DPECs are enriched in Randall's plaque tissue. Finally, cell-to-cell communication revealed that Loop of Henle, DPECs and osteoblasts-associated macrophages were the main source of SPP1 signaling. Our work will further the understanding of the microenvironment among Randall's plaque tissues and provide deep insight into immune modulation.