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

Randall9s plaque is significantly associated with the occurrence of nephrolithiasis. However, the microenvironment of Randall9s plaque is poorly characterized. To investigate the microenvironment of Randall9s plaque, we analyzed single-cell RNA data of 3 Randall9s plaque and 3 normal renal papillae tissue and identified 11 different cell types. We screened differentially expressed genes among all cell types between Randall9s 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 macrophage M1/M2 imbalance. Notably, we detected ossification-associated macrophage is enriched in Randall9s plaque and validated GPNMB and ACP5 were potential biomarkers on the ossification-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 Randall9s plaque tissue. Finally, cell-to-cell communication revealed that Loop of Henle, DPECs, and osteoblasts-associated macrophages was the main source of SPP1 signaling. Our work will further the understanding of the microenvironment among Randall9s plaque tissues and provide deep insight into immune modulation.