Single-cell sequencing reveals peritoneal environment and insights into fibrosis in CAPD patients.

Abstract

Long-term peritoneal dialysis (PD) is associated with the development of peritoneal fibrosis (PF). Understanding the changes of immune environments and peritoneal mesothelial cells (PMCs) may lead to the discovery of mechanisms of PF. Therefore, we used single-cell RNA sequencing to interrogate cell composition and transcriptome characteristics in dialysate of continuous ambulatory PD (CAPD) patients at different stages. Results showed that six major cell populations were identified in overnight effluent dialysate. Two subsets of macrophages (Macro-c2-SSP1 and Macro-c5-FCN1&SSP1) and PMCs (HSPA1A+ PMCs and RPL34+ PMCs) had the property of promoting fibrosis. Long-term patients had higher markers of cytotoxic CD8+T cells. Moreover, the expression levels of fibrosis-related genes were significantly increased and PMCs interacted closely with immune cells in the long-term group (p<0.05). These data reveal new phenotypes and functional characteristics of immune cells and PMCs in dialysate of CAPD patients with different stages, which provide potential mechanisms and therapeutic strategies for PF.