Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the deve...Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.展开更多
基金supported by the Hunan Provincial Natural Science Foundation for Outstanding Youth(China)(No.2022JJ10093,2020JJ2020)the Scientific Research Fund of Hunan Provincial Health Commission(China)(No.B202303056777)+1 种基金the Major Research and Development Program of Hunan Province,China(No.2020SK2116)the Key Program of Hunan Provincial Health Commission(China)(No.202203052969).
文摘Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.